No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Mycoplasma pulmonis in Rats
... The entry of mycoplasma infection into the laboratory animals can be prevented by focusing on the entry of animals and the biological materials inside the laboratory animal houses, therefore the laboratory animals should be procured from reputed vendors, quarantined and screened prior to introducing into the laboratory animal house (Graham et al. 2011). The strategies such as proper cleaning and sanitation of laboratory animal houses, cages, feeders and waterers and segregation of diseased/ill laboratory animals from a healthy animal should be followed (Fox et al. 2002). ...
... Depopulation of infected colonies may also be helpful in the prevention of laboratory animal mycoplasmosis. The control of environmental conditions, which are favourable for the development of the mycoplasma infection in laboratory animals (Like frequent sanitation of cages and reduction in the population density of laboratory animals inside the cages to reduce the ammonia level inside the cages) may also reduce the risk of laboratory animal mycoplasmosis outbreak (Graham J E et al. 2011). ...
... The solid-bottom cages for rodents should be changed 2-3 times in a week whereas for rabbits, rodents, and nonhuman primates in suspended cages over excreta pans and for mice in a ventilated cage system, cage changes at alternate week will be sufficient. In case of larger animals daily removal of excreta and soiled bedding material, and daily cleaning and sanitization of primary enclosures will be helpful in prevention of laboratory animal diseases (Graham et al. 2011). ...
Mycoplasmas are the smallest, free-living, cell wall less prokaryotes from the class mollicutes, and these are relatively slow-growing microorganisms. Most of the laboratory animals may get the mycoplasma infection naturally. A large number of mycoplasma species (Mycoplasma pulmonis, M. muris, M. neurolyticum, M. collis, M. arthritidis and M. caviae etc.) have been reported from the laboratory animals. These are responsible for the development of a large numbers of clinical conditions in laboratory animals hence they may cause interference in the results of ongoing research/experimental works on those laboratory animals. This review article gives insights on laboratory animal mycoplasma infections including pathogenesis, clinical signs, lesions, diagnosis, and interference in the experimental work, prevention, and control.
... In particular, respiratory issues were reported by a majority of owners. While this finding might reflect that many (> 90% 36 ) pet rats will carry mycoplasma which causes such issues and is difficult to control or eliminate, 36 the environment and diet of the rat has been shown to contribute to disease outcome. 36 In particular, increased ammonia levels, poor ventilation, pine and cedar bedding substrate, and nutritional deficiencies have been associated with poorer disease outcome. ...
... While this finding might reflect that many (> 90% 36 ) pet rats will carry mycoplasma which causes such issues and is difficult to control or eliminate, 36 the environment and diet of the rat has been shown to contribute to disease outcome. 36 In particular, increased ammonia levels, poor ventilation, pine and cedar bedding substrate, and nutritional deficiencies have been associated with poorer disease outcome. 36 Although the total number of rats was a predictor of respiratory issues, it is unclear whether this directly relates to the rats' environment (e.g. a greater number of rats leading to a greater build-up of ammonia and hence a greater likelihood of respiratory issues) or the likelihood of a health issue occurring in at least one rat (e.g. the probability of at least one rat in a group of six developing a respiratory issue is greater than the probability of at least one in a group of three developing a respiratory issue). ...
... 36 In particular, increased ammonia levels, poor ventilation, pine and cedar bedding substrate, and nutritional deficiencies have been associated with poorer disease outcome. 36 Although the total number of rats was a predictor of respiratory issues, it is unclear whether this directly relates to the rats' environment (e.g. a greater number of rats leading to a greater build-up of ammonia and hence a greater likelihood of respiratory issues) or the likelihood of a health issue occurring in at least one rat (e.g. the probability of at least one rat in a group of six developing a respiratory issue is greater than the probability of at least one in a group of three developing a respiratory issue). ...
Background:
To date, despite the substantial literature investigating how rats prefer to be kept in captivity, no research has been conducted to assess the housing, husbandry and health of pet rats.
Methods:
To better understand the United Kingdom's pet rat population and the welfare issues they face, we conducted an online survey of pet rat owners. The survey included questions about the owner and their opinions about pet rats, and about their rats' health, husbandry and housing.
Results:
The results, from 677 complete responses, highlighted areas of rat care that were "good", "bad" and "ugly" (i.e. likely to be highly detrimental to welfare). The good was that many rats were provided with a social companion and enrichment; the bad was that we could not be certain whether rats had a sufficiently nutritious diet or sufficient opportunities to explore or adequate nesting substrate; and the ugly included cases of exposure of rats to predator species within the home and a generally high prevalence of disease.
Conclusions:
We conclude that there is much cause for concern about the welfare of pet rats in the United Kingdom.
... This disease frequently goes undiagnosed due to subclinical nature. MP is transmitted vertically through the placenta and horizontally through direct contact or aerosol [3,4], and thus, it is difficult to get rid of disease without following all-in-all-out policy. ...
... It becomes important to diagnose MP infection due to its potential interference with a wide variety of research. Commonly observed clinical signs include sneezing, nasal discharge with dyspnea or rales, and also torticollis in the case of middle/internal ear infection [4,5]. Other common signs of disease such as weight loss, hunched posture, ruffled coat, and chromodacryorrhea may also be observed [1,2]. ...
... Commonly used diagnostic procedures include serology, culture, histopathology, and polymerase chain reaction (PCR) [4,9]. In this study, we report a detailed study of clinical symptoms, postmortem lesions, and diagnosis of MP infection in a rat colony. ...
Aim: Mycoplasma pulmonis (MP) remains potentially important rodent pathogen causing murine respiratory mycoplasmosis (MRM) which may go undiagnosed due to its asymptomatic nature. In the present study, we carried out clinical, pathological, and molecular investigations of MP-induced MRM in a rat colony.
Materials and Methods: Two female Wistar rats were observed to be diseased in animal facility of NISER, Bhubaneswar, and were kept in isolation for further investigation. Both the animals were found to be positive for MP after serological and molecular tests. Thereafter, whole rat colony comprising of 36 animals was segregated based on clinical symptoms and further sampled for histopathological, serological, and molecular investigations. Tracheal washing and infected lung tissue were collected during necropsy examination for DNA extraction. Molecular diagnosis was done by polymerase chain reaction (PCR) assay using species-specific primers.
Results: Classical symptoms of MP-associated respiratory tract infection were observed in only 2 of 36 infected animals, and most of the animals were found asymptomatic to the disease; however, all the animals were found to be carrier after necropsy and PCR assay. Gross and histopathological finding suggested severe congestion of the lungs along with suppurative and necrotizing pneumonia. The disease is confirmed by molecular diagnosis using species-specific primers in PCR assay.
Conclusion: MRM may go undiagnosed due to asymptomatic nature. Detailed study of clinical symptoms, pathology, serology, and PCR-based molecular approach may aid in health monitoring and detection of MRM in a rodent colony reared for experimental purpose.
... diseases in companion rats. 1,2 Pneumonia may be associated with Mycoplasma pulmonis, ciliary associated respiratory bacteria, Streptococcus pneumoniae, Corynebacterium kutscheri, the fungus Pneumocystis carinii, sialodacryoadenitis coronavirus, Sendai virus, murine pneumonia virus, and paramyxoviruses among others. 3,4 Laboratory rats are typically tested for these infectious diseases 5 but systematic testing is not performed in companion rodents 4 and these agents are often present concomitantly and may act synergistically. ...
... 2,6 Thoracic lesions due to infectious agents can lead to dyspnea, which is a common cause of presentation of rats to exotic practitioners. 1,7 Conversely, spontaneous thoracic neoplasms are rare 7,8 and may be misdiagnosed. 9 Rats are used as model for carcinogen-induced pulmonary tumors in humans, 10 and the most common primary pulmonary tumors of rats are alveolar adenomas and carcinomas arising from type II pneumocytes 7,8,[10][11][12] and Clara cells. ...
... 3 Some authors have postulated that thoracic radiographs may be useful for differentiating mycoplasmosis from thoracic neoplasms in companion rats. 1 In dogs, the distribution of lesions among lobes may give an indication of the possible nature of pulmonary neoplasms. 17 In addition, in domestic carnivores, a solitary well-defined pulmonary nodule and multiple circumscribed nodules or masses are considered imaging signs of pulmonary neoplastic diseases. ...
Companion rats are often presented to veterinarians for respiratory difficulties. Dyspnea in rats is most commonly due to infectious pneumonia, and thoracic neoplasia can go undiagnosed ante mortem due to a mistaken interpretation of pneumonia. In domestic carnivores, pulmonary nodular patterns have been shown to correlate with lung neoplastic diseases and infectious diseases. The main objective of this retrospective case series study was to determine whether certain radiographic criteria could be correlated with the presence of thoracic infectious disease and neoplastic disease in companion rats. A secondary objective was to determine whether the patient's sex and age were different between rats diagnosed with infectious versus neoplastic disease. Medical records and thoracic radiographs of dyspneic companion rats presented to the University of California at Davis, William R. Pritchard Veterinary Medical Teaching Hospital during the time period from January 2000 to December 2014 were reviewed. Rats with postmortem confirmation of thoracic lesions were included in the study. Thoracic radiographs were evaluated for positioning, lesion distribution, lung lobe involved, pulmonary pattern, mediastinal and pleural lesions by three observers blinded to diagnosis. Thirty rats were included in the study, including 23 rats with an infectious disease and seven with neoplasia. Mediastinal lesions were significantly more prevalent in the group diagnosed with thoracic neoplasia (P = 0.031), in particular cranially (P = 0.048). Although there was an overlap between the two groups, findings indicated that the presence of cranial mediastinal lesions may be helpful for differentiating neoplastic from infectious disease in rats.
... Although rats can be affected at any age, clinical signs are usually noticed in older animals whereas the disease is often silent in younger ones. 1 Most commonly observed lesions associated with CRD include suppurative rhinitis, otitis media, suppurative bronchopneumonia, atelectasis, bronchiectasis, and pulmonary abscesses. 4 Antibiotics are the primary treatment for CRD in rats. 1 Additional treatments including expectorants, anti-inflammatory drugs, and bronchodilators can improve clinical signs. 4 In the treatment of respiratory disease, the lung is an attractive target for drug delivery compared to other systemic routes of administration. ...
... 4 Antibiotics are the primary treatment for CRD in rats. 1 Additional treatments including expectorants, anti-inflammatory drugs, and bronchodilators can improve clinical signs. 4 In the treatment of respiratory disease, the lung is an attractive target for drug delivery compared to other systemic routes of administration. Recommendations for drug aerosol delivery in rats with CRD exist in popular literature, 5,6 veterinary journals, 4,7,8 conference proceedings, [9][10][11] and exotic animal textbooks. ...
Vestibular signs are rarely reported in ferrets. This report documents the successful diagnosis and management of an otitis interna without otitis media in a ferret. A 4-year-old deslorelin-implanted female ferret presented with an acute-onset, 2-day history of circling and falling to the right, and a diminished appetite. Neurologic examination revealed a right-sided head tilt associated with bilateral horizontal nystagmus, which had a fast phase to the left. These findings strongly suggested a right-sided vestibular syndrome. A complete blood cell count, serum biochemistry panel, and CT scan were unremarkable. A 1.5T contrast-enhanced magnetic resonance imaging scan of the brain showed a hypointense T2 signal abnormality of the right inner ear, without the involvement of the middle ear. The lesion showed contrast enhancement after contrast media administration in T1 sequence. The final diagnosis was otitis interna. The ferret was hospitalized and received intravenous fluids, oral enrofloxacin, and prednisolone. Clinical signs rapidly improved with treatment and the ferret was discharged after 5 days in the hospital. Treatment was continued for a further 15 days. Six months later, the ferret was healthy and not displaying any neurologic signs. Otitis interna should be included in the differential diagnosis for peripheral vestibular syndrome in ferrets. This case report highlights the importance of advanced imaging techniques to reach a definitive diagnosis.
... Although rats can be affected at any age, clinical signs are usually noticed in older animals whereas the disease is often silent in younger ones. 1 Most commonly observed lesions associated with CRD include suppurative rhinitis, otitis media, suppurative bronchopneumonia, atelectasis, bronchiectasis, and pulmonary abscesses. 4 Antibiotics are the primary treatment for CRD in rats. 1 Additional treatments including expectorants, anti-inflammatory drugs, and bronchodilators can improve clinical signs. 4 In the treatment of respiratory disease, the lung is an attractive target for drug delivery compared to other systemic routes of administration. ...
... 4 Antibiotics are the primary treatment for CRD in rats. 1 Additional treatments including expectorants, anti-inflammatory drugs, and bronchodilators can improve clinical signs. 4 In the treatment of respiratory disease, the lung is an attractive target for drug delivery compared to other systemic routes of administration. Recommendations for drug aerosol delivery in rats with CRD exist in popular literature, 5,6 veterinary journals, 4,7,8 conference proceedings, [9][10][11] and exotic animal textbooks. ...
Most pet rats have chronic respiratory disease, and end-stage complications are frequently fatal. Drug aerosol delivery in the form of nebulization of antibiotics, expectorants, and bronchodilators is often used as part of their treatment. As rats are obligate nasal breathers, aerosol delivery must be achieved by nasal inhalation, which has the anatomical limitation of a narrower airway lumen. In humans, aerosol delivery of many respiratory drugs is achieved by oral inhalation as it allows administration of very small particles with a concentration loss of only 20% in comparison with 85% by the nasal route. The aim of this pilot study was to determine whether a nebulized fluorescein solution would reach the lungs of rats as no data exists. Ten healthy 13-week-old female Sprague-Dawley rats were nebulized continuously for 15 minutes. The rats were euthanized, and a full postmortem examination was performed. The respiratory tract was sampled, fast-frozen in liquid nitrogen and preserved at −20 °C. Slides were examined with a fluorescence microscope to determine the distribution of fluorescein in the respiratory tract. Fluorescence was observed in the entire respiratory tract of all the nebulized rats, showing that nebulization is an efficient way to deliver medication directly into the alveoli.
... The second challenge is that an individual owner's understanding of what good housing and husbandry entails will likely be influenced by their experiences of and beliefs about the species. [13][14][15] In the case of rats, this may include factors such as knowledge of rat ecology, 16,17 familiarity with core welfare principles like the five freedoms, 18,19 the sorts of husbandry-related injuries that appear in veterinary practices, [20][21][22] and observations of rats in their home environment and the sorts of activities and enrichment that attract the most interest. 7,23 Consultation with multiple experts can help to surmount these challenges; consensus methods are considered to be particularly useful when there is little empirical evidence, and they also capitalise on multiple minds (and experiences) being better than one. ...
Background:
Pet care guidelines play an important role in ensuring that owners are well informed about good husbandry practices, allowing them to provide the best care for their animals. However, the development of such guidelines is difficult when there is little appropriate empirical evidence on which to base guidelines, as in the case of pet rats. The consultation of multiple experts can help to surmount this challenge.
Methods:
We developed a set of guidelines for pet rat housing by consulting with a group of experts, including veterinarians, veterinary nurses, animal welfare scientists and experienced pet rat owners. The consultation involved two rounds of online surveys (n = 13) and one online discussion (n = 8).
Results:
The resulting guidelines cover a broad range of features within pet rat housing, including injury prevention, details of suitable refuges and substrates, and suitable cage sizing. The guidelines may evolve as more information about pet rats comes to light but may nonetheless provide a useful starting point for any future guidelines.
Conclusions:
At present, these guidelines may not only be useful for pet rat owners and those advising pet rat owners, such as veterinarians, but may also be useful in the design of housing, including for laboratory rodents.
A mammal harbours a vast number of microorganisms in the form of bacteria, viruses, protozoans, parasites, fungi and archaea, which is known as the microbiota. The animal host contains approximately 20,000 genes, while the microbiota contains more than 1 million genes. Therefore, many of the competences of a laboratory animal have arisen from the microbiota rather than the mammal genome. As there is substantial variation in composition between animals, animal units and commercial production sites and little information available on this, it is a challenge for experimental design, reproducibility and translatability of animal experiments. Some of the microorganisms are pathogens, i.e. they can induce spontaneous clinical disease in the animals, while others are commensals, i.e. their presence is latent. Traditionally, pathogens have been eradicated from so-called specific pathogen-free breeding colonies of research rodents to decrease mortality, disease incidence, inter-individual parameter variation and other forms of research interference. However, today it can also be argued that animals which have never been infected with pathogens have an under-stimulated immune system and, therefore, may be less translational compared to humans. Many of the commensals have been shown to be important for the induction of animal models, and variation in microbiota composition is responsible for a substantial part of the inter-individual variation in responses of many models and for different outcomes in different facilities. It is still a good principle that rodents for research only are bought from colonies bred behind a specific pathogen protecting barrier and that they are subjected to current health monitoring, which should be documented. However, it can also for individual studies be necessary to include a characterization of the microbiota, which has been made possible by modern sequencing techniques, which over the last decade have become more efficient and cheaper. Characterization can be done on a colony level, but eventually it can also be done on all animals in a specific study, which will allow the incorporation of the information in the data evaluation. It may also be important to ensure that specific bacteria needed for a proper model expression are present in the animals to be used. Before progressing from preclinical animal studies to clinical human studies, it might be considered wise to supplement the studies in SPF animals with animals infected with pathogens.
Diagnostic imaging is commonly necessary for the evaluation of emergency presentations. As for other species, veterinarians often rely on radiography and ultrasonography, and to some extent on computed tomography and magnetic resonance imaging, to achieve a clinical diagnosis and provide the highest standard of care possible. This chapter reviews the applications of diagnostic imaging on exotic animal emergencies.
Management of epizootics of exotic companion mammal herds relies on careful observance of animals, proper management and husbandry, adequate nutrition, and stress reduction. Many diseases occur because of the stress of weaning so anticipating this and maximizing sanitation and ventilation, minimizing overcrowding and concurrent disease, and providing enough fiber for herbivores is prudent. Antimicrobial therapy must be carefully considered in the route of administration and the likely risk of enterotoxemia development. Separation of affected animals, rapid diagnostic testing, and implementation of treatment and supportive care minimizes losses during epizootics. Knowledge of potential zoonotic pathogens is important for veterinarians and staff.
Ferrets, rabbits, and other exotic companion mammals are often admitted to animal shelters. It is imperative for shelters to be aware of the unique anatomic features, husbandry requirements, and safe handling techniques for these species. This chapter reviews some of the most important aspects of appropriate care for these animals in a shelter setting. Ferrets are social animals and are ideally housed with other ferrets. Ferrets are predators and the odors of ferrets can be stressful to prey species like rabbits and rodents; it is important to house ferrets away from these species. Rabbits are social animals and can be housed in pairs or small groups if they are neutered and have personalities compatible with conspecifics. Housing rabbits away from dogs, cats, ferrets, and guinea pigs is recommended to avoid exposure of these species to B. bronchiseptica.
The aim of this study was to evaluate the number of mast cells in healthy and affected lungs of mice and rats and determine histopathological differences of the inflammatory process in the lungs of rats and mice. The lungs of healthy and affected laboratory mice (n = 80) and rats (n = 80) were used for the studies. The histpathological examination of HE slides was performed. The number of mast cells in healthy and affected lungs of mice and rats was calcaluted in Giemsa stained slides. The number of connective tissue mast cells in healthy animals and in areas of lymphoid hyperplasia and bronchiectasis was significantly higher in rats than in mice. Interstitial pneumonia with bronchiolitis and bronchiectasis and atelectasis was more expressed in rats (P = 0.006-0.025) than in mice. Lymphoid tissue hyperplasia in the lungs of mice was found much more intense than in rats (P = 0.011). In affected laboratory mice and rats Mycoplasma pulmonis was identified. Interstitial pneumonia with bronchiolitis and bronchiectasis and atelectasis were more pronounced in rats. In our opinion, because healthy rats have more mast cells in the connective lung tissue and developed more severe pneumonia, they had a higher response of mast cells to the inflammatory process compared to mice. There was a more intense lymphocytic response in the lungs of mice.
Veterinary practitioners who care for small mammal pets, such as rabbits, rodents, and ferrets, face several challenges when using antimicrobial medications in these species. Drug dosages are generally based on extrapolation from other species and/or clinical experience, and many pharmacokinetic studies performed in these animals are actually models for human trials. This chapter discusses these many challenges in more detail, and concludes with a series of tables listing some reported dosages of antimicrobials, and common conditions in small mammal pets. Administration of antimicrobials in these prey species must be performed in a way that allows for the entire dose to be given without unduly stressing the patient. It is important to recognize that, in addition to prescribing antimicrobial therapy in small mammal patients, and demonstrating the correct method of administration to ensure compliance, veterinarians must also advise clients on correct management, nutrition, and husbandry practices.
This chapter reviews the pertinent microbiological, pathological, diagnostic, and medical features of naturally occurring bacterial, mycoplasmal, and mycotic infections occurring bacterial, mycoplasmal, and mycotic infections of the laboratory rat. Several bacterial infections discussed in the chapter are streptobacillosis, spirochetosis, Streptococcus pneumoniae infection, Enterococcus sp. infection, pseudomoniasis, Clostridium piliforme infection, Corynebacterium kutscheri infection, Salmonella sp. infection, and pasteurellaceae infection. Several mycotic infections discussed are dermatomycosis, deep mycoses, and pneumocystosis. Several mycoplasmal and rickettsial infections presented are respiratory mycoplasmosis, genital mycoplasmosis, and articular mycoplasmosis. There are several organisms isolated occasionally in the course of health surveillance with rats that are difficult to categorize as to pathogenicity and that do not recur often enough either as commensals or in periodic association with disease states as to be regarded as natural pathogens of the rat. Clinical conditions caused by such organisms as Bordetella bronchiseptica, Klebsiella pneumoniae, K. oxytoca, and Staphylococcus aureus fall within this group and might, more properly, be regarded as infections.
Angiogenesis and lymphangiogenesis participate in many inflammatory diseases, and their reversal is thought to be beneficial. However, the extent of reversibility of vessel remodeling is poorly understood. We exploited the potent anti-inflammatory effects of the corticosteroid dexamethasone to test the preventability and reversibility of vessel remodeling in Mycoplasma pulmonis-infected mice using immunohistochemistry and quantitative RT-PCR. In this model robust immune responses drive rapid and sustained changes in blood vessels and lymphatics. In infected mice not treated with dexamethasone, capillaries enlarged into venules expressing leukocyte adhesion molecules, sprouting angiogenesis and lymphangiogenesis occurred, and the inflammatory cytokines tumor necrosis factor and interleukin-1 increased. Concurrent dexamethasone treatment largely prevented the remodeling of blood vessels and lymphatics. Dexamethasone also significantly reduced cytokine expression, bacterial burden, and leukocyte influx into airways and lungs over 4 weeks of infection. In contrast, when infection was allowed to proceed untreated for 2 weeks and then was treated with dexamethasone for 4 weeks, most blood vessel changes reversed but lymphangiogenesis did not, suggesting that different survival mechanisms apply. Furthermore, dexamethasone significantly reduced the bacterial burden and influx of lymphocytes but not of neutrophils or macrophages or cytokine expression. These findings show that lymphatic remodeling is more resistant than blood vessel remodeling to corticosteroid-induced reversal. We suggest that lymphatic remodeling that persists after the initial inflammatory response has resolved may influence subsequent inflammatory episodes in clinical situations.
Mycoplasma pulmonis causes chronic murine respiratory mycoplasmosis and genital disease in rats. Specific immunoglobulin M (IgM), IgA, and IgG and its subclasses present in sera and tracheal and uterine lavage samples from 36 naturally infected Sprague-Dawley female rats were tested for reactivity with M. pulmonis in an enzyme-linked immunosorbent assay. Ten specific-pathogen-free Sprague-Dawley female rats served as the negative controls. Tracheal and uterine lavage samples were cultured quantitatively for M. pulmonis. M. pulmonis was isolated from the trachea (35 of 36) and uterus (17 of 36) of naturally infected rats; all rats were infected in at least one of the two sites cultured. M. pulmonis was not isolated from any control rat. There was a significant difference in levels of specific antibody of all classes except IgG2c between control and naturally infected animals (P less than 0.001 for IgM, IgG, IgG1, and IgG2a; P less than 0.002 for IgG2b; and P less than 0.02 for IgA). There was no correlation between numbers of M. pulmonis cells isolated and the amount or class of antibody measured in serum or tracheal lavage specimens. The predominant antibodies to M. pulmonis found in the sera of naturally infected rats were IgG and IgM. The IgG2a subclass was responsible for the majority of IgG-positive animals. There were no differences between rats which were positive by culture for M. pulmonis in the uterus (U+) and rats which were negative by culture for M. pulmonis in the uterus (U-) with respect to distribution or amount of antibody classes and subclasses in the serum. However, tracheal wash samples from U+ rats had significantly higher (P less than 0.03) levels of specific IgG1 and IgG2a than those from U- rats. Conversely, IgG2a was present in higher levels in pooled uterine lavage specimens from U- rats than in those from U+ rats.
The mouse model of acute murine respiratory mycoplasmosis was used to screen 18 strains of Mycoplasma pulmonis for their ability to establish respiratory infections and produce gross lung lesions in the susceptible C3H/HeN mouse strain. All experiments were designed to minimize host, environmental, and microbial differences to ensure that experimental results would reflect differences in mycoplasmal virulence. There were differences in the 50% infectious dose (range, 3 X 10(2) to greater than 10(7) CFU) and the 50% gross pneumonia dose (range, 10(3) to greater than 10(7) CFU) among the 18 mycoplasmal strains. Only 10 strains (UAB CT, M1, UAB 5782C, UAB 6510, 66, UAB T, UAB 8145D, Nelson C, Peter C, and Negroni) established respiratory infections, and only 2 of the 10 strains (UAB CT and M1) produced gross lung lesions. Strains UAB CT, UAB T, M1, UAB 5782C, and PG34(ASH) were chosen for qualitative and quantitative evaluation of lung lesions in C3H/HeN and C57BL/6N mice. Lesion incidence and severity was dependent on the mycoplasmal strain and the mouse strain. Microscopic lesions varied among mycoplasmal strains and mouse strains in the amount of lymphoid infiltrate, neutrophilic exudate, and consolidation, as well as overall severity. The most virulent strain, UAB CT, produced acute pneumonitis in the 10(7) CFU dosage group and required a threshold dose of 10(3) CFU to consistently produce microscopic lung lesions. These results suggest that M. pulmonis virulence is multifactorial and different strains of mycoplasmas yield disease expressions that differ both qualitatively and quantitatively.
Isolation, indirect immunofluorescence, an enzyme-linked immunosorbent assay (ELISA), and histopathological examination of tissues for characteristic lesions were evaluated for their efficiency in detecting Mycoplasma pulmonis infection in rats. Whereas all of the methods were efficient in naturally infected Sprague-Dawley rats, none of the methods consistently detected infection in F344 rats experimentally infected with low doses of the organism. In the experimental infections, however, the success rate of any method was directly related (P less than 0.05) to increasing inoculum dose and time postinoculation. Collectively, the data indicated that isolation of M. pulmonis was the most efficient single detection method and the nasopharyngeal duct was the best single site to culture, although sampling of multiple sites within the respiratory tract increased the rate of isolating the organism. The ELISA was understandably the least sensitive method in the low-dose, experimentally infected rats because of the time required for development of a detectable serum antibody response. Although each of the four methods identified a high percentage of naturally infected rats, the ELISA was the most efficient method in these animals as it was uniformly positive. The use of combinations of methods was found to increase the rate of detection of M. pulmonis infection in both experimentally and naturally infected rats.
Ammonia (NH3) from soiled cage bedding is known to enhance the progression and severity of murine respiratory mycoplasmosis in rats. To test the hypothesis that NH3 directly or indirectly enhances the growth of Mycoplasma pulmonis in vivo, pathogen-free F344 rats were inoculated intranasally with 1 x 10(4) to 4 x 10(4) or 4 x 10(6) to 5 x 10(6) colony-forming units of M. pulmonis and exposed to less than or equal to 1.5 or 76 microgram of NH3 per liter (less than or equal to 2 or 100 ppm, respectively). Nasal passages, larynges, tracheas, and lungs from rats killed at intervals up to 28 days after inoculation were quantitatively cultured. Growth of M. pulmonis was much greater in NH3-exposed rats than in controls, particularly in those inoculated with the lower dose. Increases in M. pulmonis populations were more rapid in proximal airways than in distal airways. Serum immunoglobulin G and M antibody responses to M. pulmonis as measured by an enzyme-linked immunosorbent assay were greater in NH3-exposed rats. In other experiments, the nasal passages absorbed virtually all NH3 when the rats were exposed to less than 380 micrograms of NH3 per liter (500 ppm), indicating that NH3 induced increases in the numbers of organisms in the distal respiratory tract, probably by a secondary, rather than a direct, effect. Also, NH3 exposure did not inhibit pulmonary antibacterial activity as measured by clearance of radiolabeled Staphylococcus epidermidis. The growth of M. pulmonis in vitro was inhibited by 1 mM NH4+ added to the medium as NH4OH but not by NH4+ concentrations of 0.5, 0.1, or 0.01 mM, suggesting that NH3 increases growth indirectly through effects on the host.
Specific-pathogen-free (SPF) female Sprague-Dawley rats were infected by intravaginal inoculation with 3 x 10(7) CFU of Mycoplasma pulmonis X1048 in 0.1 ml of Frey's broth or with an equal volume of sterile Frey's broth. A minimum of 10 days postinfection, rats were bred to noninfected males. Rats were necropsied at days 11, 14, and 18 of gestation and within 24 h of parturition. Throughout pregnancy, at least 50% of rats remained infected in the lower genital tract. At parturition, the major site of colonization was the respiratory tract (P = 0.02). M. pulmonis was not isolated from any site of any control rat. Pregnancy outcome was adversely affected by infection with M. pulmonis. Infected rats had significantly smaller litter sizes at day 18 of gestation (P < or = 0.01) and at term (P < or = 0.004). No statistically significant differences among the gestational stages in infected rats were noted for litter size. Total litter weight is a reflection of individual pup weight and of the number of pups born. Therefore, it was obvious that infected rats would have a significantly lower (P < or = 0.008) total litter weight than noninfected controls. However, when individual pup weights were considered, infected pups (n = 49) also had significantly lower (P < or = 0.0001) birth weights than did noninfected controls (n = 68). The incidence of an adverse pregnancy outcome at term (stillbirths, macerated fetuses, or resorptions) was higher (P < or = 0.01) in infected rats than in noninfected control rats. No stillborn pups or macerated fetuses were observed in any control term rats (n = 5). All control rats had live-born pups. Three infected rats had no live-born offspring. Resorptions were more common in infected rats than in control rats (P < or = 0.01). The mean number of resorptions per rat was greater in rats which went to term than in rats necropsied during gestation, indicating that the severity of disease was progressive. The rat is frequently the laboratory animal of choice for a wide variety of reproductive studies, and the experimental parameters that are most often measured (litter size, pup weight, and neonatal survival) were all adversely affected by genital mycoplasmosis. Genital mycoplasmosis is important as an animal model for the interaction of infectious agents and the host during pregnancy as well as in its own right as a confounding variable affecting research projects which use the rat as a model to study reproductive function and physiology.
Genital mycoplasmosis is important as an animal model for the interaction between infectious agents and the host during pregnancy as well as in its own right as a confounding variable affecting research projects in which the rat is used as a model to study reproductive function and physiology. We report the in utero transmission of Mycoplasma pulmonis and the development of placentitis, amnionitis, and mild fetal bronchopneumonia in Sprague-Dawley rats. A minimum of 10 days prior to breeding, specific-pathogen-free female Sprague-Dawley rats were infected by intravaginal inoculation with 3 x 10(7) CFU of M. pulmonis X1048 or with an equal volume of sterile broth. Rats and fetuses were subjected to necropsy at days 11, 14, and 18 of gestation. M. pulmonis was able to invade the placenta, cross the placental barrier, and establish an amniotic fluid infection by gestational day 14. It was isolated from the oropharynx and lungs of fetuses at gestational day 18. The placenta was more frequently colonized than amniotic fluid, followed by the fetal oropharynx and lungs, supporting an ascending route of infection. Histopathological evidence also support an active infection, with lesions compatible with placentitis, amnionitis, and mild fetal bronchopneumonia. M. pulmonis can traverse the placenta, resulting in infection of the amniotic fluid and in utero transmission of the microorganism to the developing fetus.
Under current practices of mouse colony maintenance, sera from mice are analyzed for antibodies against several widespread infectious pathogens by conventional immunoassays, generally enzyme-linked immunosorbent assay (ELISA). To test for multiple agents, these methods consume large volumes of mouse serum and are laborious and time-consuming. More efficient immunoassays, using small amounts of sample, are therefore needed. Accordingly, we have developed a novel multiplex diagnostic system that employs fluorescent microbeads, coated with purified antigens, for simultaneous serodetection of 10 mouse infectious agents. Individually identifiable, fluorescent microbeads were coated with antigens from Sendai virus, mouse hepatitis virus, Theiler's mouse encephalomyelitis virus/GDVII strain, mouse minute virus, mouse cytomegalovirus, respiratory enteric orphan virus (Reo-3 virus), mouse parvovirus, calf rotavirus for epizootic diarrhea virus of infant mice, vaccinia virus for ectromelia virus, and Mycoplasma pulmonis. Standard sera, singly positive for antibodies to individual infectious agents, were generated by inoculation of BALB/cj and C57BL/6j mice. Sera from these experimentally infected mice, as well as sera from naturally infected mice, were analyzed using a mixture of microbeads coated with antigens of the 10 infectious agents listed above. Results demonstrated that the multiplex assay was at least as sensitive and specific as ELISA for serodetection. Importantly, the multiplex assay required only 1 microliter of serum for simultaneous serodetection of the 10 mouse infectious agents in one reaction vessel. Thus, this multiplex microbead assay is a reliable, efficient, and cost-effective diagnostic modality that will impact serosurveillance of mice used in research.
Some affected rats have mucopurulent nasal exudate or pink, porphyrin-tinted oculonasal discharge, but gross lesions in the upper respiratory tract are, in many cases, not detectable. Exudate can sometimes be found in the nasal passages, trachea, and tympanic cavities. These structures should be disturbed as little as possible during dissection and collection of specimens for culture so as to preserve the quality of the tissues for microscopic examination.
Synonyms. Murine chronic respiratory disease, infectious catarrh, chronic murine pneumonia, enzootic bronchiectasis
This chapter discusses the diseases of the respiratory system in mice, such as murine respiratory mycoplasmosis (MRM), Klebsiellosis, Pasteurellosis, Chlamydial pneumonitis, and Corynebacteriosis. Mycoplasma pulmonis is a bacterium of the sterol-requiring family Mycoplasmataceae. Like other members of the class Mollicutes, it lacks a cell wall and has a single outer limiting membrane. Although it exhibits extreme pleomorphism, ultrastructural studies have shown it to be predominantly spherical in shape and 600–1500 nm in diameter. The mechanisms by which M. pulmonis causes disease are incompletely understood, although a wide range of possibilities have been advanced. The organism is an extracellular pathogen that attaches or adheres to host-cell membranes as an initial event in infection. Klebsiella pneumoniae is widely disseminated in nature, soil, and water, as well as in agricultural and forest products. It also occurs commonly in the intestinal tract of man and animals. Pathogenic serotypes apparently are much more restricted in prevalence. P. pneumotropica is an opportunist that plays a role in respiratory tract disease only under certain circumstances.
IntroductionAnatomic FeaturesBibliography For Introduction and Anatomic FeaturesViral InfectionsBibliography For Viral InfectionsBacterial and Mycotic InfectionsBibliography For Bacterial and Mycotic InfectionsBibliography For Parasitic DiseasesNutritional and Metabolic DisordersBibliography For Nutritional and Metabolic DisordersEnvironmental, Genetic, and Other DisordersBibliography For Environmental, Genetic, and Other DisordersDiseases Associated With AgingBibliography For Diseases Associated With AgingNeoplasmsBibliography For Neoplasms
For years the ubiquity of Mycoplasma pulmonis in rodents overshadowed its pathogenic potential. Its etiologic significance in murine chronic respiratory disease was established
only by recognition of the delicate equilibrium between organism and host. Environmental factors and genetic predisposition
of the host rather than microbial virulence are the critical determinants of disease. The prevalence of M. pulmonis is undoubtedly related to the recently demonstrated in utero transmission and the ability of the organism to colonize and
produce disease in the genital tract. The etiologic significance of Ureaplasma urealyticum in human genitourinary disease, like its murine counterpart, has been surrounded by controversy. Recent studies indicate
that only a subgroup of colonized individuals develop clinical manifestations of disease, ranging from infertility to fetal
wastage. While the natural occurrence of both respiratory and genital mycoplasmoses seriously restricts the usefulness of
rats and mice for other research purposes, they represent useful models for the study of human disease. The recognized morphologic
similarities and similar natural histories of chronic bronchitis, bronchiectasis, and emphysema in humans and of M. pulmonis respiratory disease in rats and mice make the latter a particularly useful model for study of the pathogenesis of chronic
pulmonary inflammation. At the same time, murine genital mycoplasmosis represents one of the few naturally occurring genital
tract diseases in laboratory animals and therefore makes an attractive model for elucidating those subtle host-parasite interactions
that predispose to genital disease and subsequent reproductive failure.
The mitogenic activity of Mycoplasma pulmonis towards both rat B and T lymphocytes has been demonstrated. The data summarized in this report show that spleen cells obtained from T X BM rats were extensively activated by M. pulmonis. Furthermore, M. pulmonis has been demonstrated to induce the development of antibody producing cells, as attested by the appearance of direct plaque forming cells against SRBC and TNP-SRBC in spleen cultures exposed to this mitogen. It was also demonstrated that rat thymus cells and a part of the lymph node T-cell population responding to either Con A or PWM, were stimulated by M. pulmonis, the response being weaker than that of rat B-cell populations. It was thus concluded that M. pulmonis activates both rat B and T lymphocytes. This mitogenic stimulation, however, is not equally exerted on both these populations, being strongly effective upon B cells and less so on T cells.
The mitogenic activity of Mycoplasma pulmonis has been demonstrated to reside in the membrane of this microorganism. Studies aimed at the identification of the membraneous mitogenic factor have revealed that membrane proteins are essential components of this mitogenic manifestation. In addition, it has been shown that the micro-organism's outer surface membrane proteins are responsible for mitogenic activity. It has been shown, however, that isolated membrane lipids are not mitogenic for rat lymphocytes and are not required for the membrane's mitogenic potential.
Pharmacokinetic parameters of a slow release form of oxytetracycline were determined in the rat. Triexponential pharmacokinetics were displayed after intravenous administration. The half-life of the distribution phase was 0.097 hours, the rapid elimination half-life was 3.74 hours and the slow elimination half-life was 27.26 hours. Subcutaneous and intramuscular injection resulted in a rapid elimination half-life of 6.09 and 6.02 hours, respectively. In comparison, a standard form of oxytetracycline given subcutaneously had a rapid elimination half-life of 4.22 hours. The slow release form of oxytetracycline has a half-life in the rat long enough to maintain serum levels greater than the minimum inhibitory concentration of Mycoplasma pulmonis with a dose interval of 72 hours.
Tylosin has low in vitro minimum inhibitory concentrations against Mycoplasma pulmonis but levels attainable in rat serum or lung tissue have not been reported previously. Tylosin levels in rat serum and lung tissue were determined after administration of tylosin in the drinking water. Rats were given water mixed with a commercially available preparation of tylosin base, vitamins, and dextrose. Although the calculated amount of tylosin added to the water was intended to provide a concentration of 500 mg/L, the concentration attained was 70-79 mg/L and decreased rapidly with time. Bioassay of serum and lung tissue after 1-10 days of continuous medication revealed no detectable tylosin concentrations (less than 0.1 microgram/ml) in serum, while lung tissue from all treated rats contained tylosin (means = 10.69 +/- 2.66 micrograms/gm tissue, range = 3.93 to 18.14, n = 59). These concentrations are over ten times the reported in vitro minimum inhibitory concentrations against M. pulmonis which indicates that tylosin administration in drinking water may be useful in the treatment of M. pulmonis pneumonia in rats.
Chalquest and Hayflick media with and without ammonium reineckate were compared for isolation of Mycoplasma pulmonis from the nasopharyngeal ducts, tracheobronchial trees, and middle ears of 66 naturally infected rats. The results show that 92% (366 of 396) of the samples were positive for M. pulmonis in Chalquest medium with and without ammonium reineckate and 66% (260 of 396) were positive in Hayflick medium with and without ammonium reineckate (P less than 0.001). An enhancing effect of ammonium reineckate on M. pulmonis isolation was observed only in Hayflick medium; the isolation rate was 76% (151 of 198) in Hayflick medium with ammonium reineckate as compared with 55% (109 of 198) in Hayflick medium without ammonium reineckate (P less than 0.03). No significant differences in isolation rates were observed between Chalquest medium with and without ammonium reineckate. The mean growth time of M. pulmonis on Chalquest medium was 3.4 days as compared with 5.1 days in Hayflick medium, indicating that M. pulmonis can be detected earlier on Chalquest medium than on Hayflick medium. These data indicate that Chalquest medium is superior to Hayflick medium for M. pulmonis isolation from rats.
Pathogen-free weaning rats of the LEW and F344 strains were caged together for two months to eliminate microbial and environmental differences, and then infected intranasally with 10-fold dilutions of viable Mycoplasma pulmonis. At necropsy 28 days post-inoculation, F344 rats had no gross lung lesions, even those given the maximum dose of 1.4 X 10(9) colony-forming units of M. pulmonis. LEW rats often had extensive gross lesions with a gross-pneumonia-dose50 of 1.1 X 10(7) colony-forming units/rat. Histological examination of the respiratory tract (nasal passages, larynges, tracheae, and lungs) and tympanic cavities showed both qualitative and quantitative differences in lesions between the two strains, particularly in the lungs. Hyperplasia of bronchus-associated lymphoid tissue occurred in both strains, but was more extensive in LEW rats. Atelectasis, alveolar consolidation (due primarily to mononuclear inflammatory cells), and suppurative bronchitis and bronchiolitis were seen only in LEW rats. Infiltrates of lymphoid cells into the lungs distal to bronchi and around blood vessels also were seen primarily in LEW rats. These differences between the two rat strains provide excellent model systems with which to dissect the role of cell responses in the pathogenesis of a naturally occurring chronic lung disease.
For years the ubiquity of Mycoplasma pulmonis in rodents overshadowed its pathogenic potential. Its etiologic significance in murine chronic respiratory disease was established only by recognition of the delicate equilibrium between organism and host. Environmental factors and genetic predisposition of the host rather than microbial virulence are the critical determinants of disease. The prevalence of M. pulmonis is undoubtedly related to the recently demonstrated in utero transmission and the ability of the organism to colonize and produce disease in the genital tract. The etiologic significance of Ureaplasma urealyticum in human genitourinary disease, like its murine counterpart, has been surrounded by controversy. Recent studies indicate that only a subgroup of colonized individuals develop clinical manifestations of disease, ranging from infertility to fetal wastage. While the natural occurrence of both respiratory and genital mycoplasmoses seriously restricts the usefulness of rats and mice for other research purposes, they represent useful models fo the study of human disease. The recognized morphologic similarities and similar natural histories of chronic bronchitis, bronchiectasis, and emphysema in humans and of M. pulmonis respiratory disease in rats and mice make the latter a particularly useful model for study of the pathogenesis of chronic pulmonary inflammation. At the same time, murine genital mycoplasmosis represents one of the few naturally occurring genital tract diseases in laboratory animals and therefore makes an attractive model for elucidating those subtle host-parasite interactions that predispose to genital disease and subsequent reproductive failure.
Murine respiratory mycoplasmosis (formerly murine chronic respiratory disease) has been conclusively shown to be due to Mycoplasma pulmonis. Based upon experimental studies, it is clear that the disease is an insidious, protracted process involving a variety of interrelated factors. Intracage NH3 (25 to 250 ppm) greatly increases disease incidence, severity and progression. In mice, the presence of other infectious agents, like Sendai virus, also potentiates disease. However, comparisons of animals matched for age, sex, microbial, and environmental factors indicate that heredity is one of the most critical determinants of disease. M. pulmonis is generally thought to be transmitted via aerosol, but recent evidence indicates that in utero transmission is also possible. M. pulmonis can colonize and produce disease in all parts of the female genital tract. While the natural occurrence of both respiratory and genital mycoplasmoses seriously restricts the usefulness of rats and mice for other research purposes, the experimental diseases represent useful models for the study of human disease, particularly mechanisms involved in chronic pulmonary inflammation and reproductive failure.
Mycoplasma pulmonis infection in rats causes a chronic inflammatory airway disease. Along with extensive remodeling of the airway mucosa, lymphocytic infiltrates, angiogenesis, and mucosal thickening, there is an abnormal sensitivity of the blood vessels to mediators that evoke "neurogenic inflammation". As a result, substance P, a peptide released from sensory nerves, produces an unusually large amount of plasma leakage. These changes can be prevented or reduced by prophylactic treatment with antibiotics, but it is unknown whether the extensive remodeling of the airway mucosa and potentiation of neurogenic inflammation can be reversed once they are established. We addressed this issue in F344 rats that were infected with M. pulmonis at 8 wk of age. Six weeks later, the rats were treated daily with an antibiotic (oxytetracycline, 20 mg/kg intramuscularly), to reduce the number of infecting organisms, or with an antiinflammatory steroid (dexamethasone, 0.5 mg/kg intraperitoneally), to reduce the inflammatory and immunologic response to the infection. Sham-treated infected rats received daily injections of 0.9% NaCl. After 1, 2, or 4 wk of treatment the rats were anesthetized and then challenged with substance P (5 micrograms/kg intravenously). The sham-treated rats had pathologic changes in their airways typical of severe M. pulmonis infection, and had as much as a threefold increase in substance P-induced plasma leakage. By comparison, after 4 wk of treatment with oxytetracycline or dexamethasone, the chronic inflammation was nearly resolved and the response to substance P was in the normal range. Unexpectedly, dexamethasone, like oxytetracycline, reduced the number of infecting organisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiogenesis and microvascular remodeling are known features of chronic inflammatory diseases such as asthma and chronic bronchitis, but the mechanisms and consequences of the changes are just beginning to be elucidated. In a model of chronic airway inflammation produced by Mycoplasma pulmonis infection of the airways of mice or rats, angiogenesis and microvascular remodeling create vessels that mediate leukocyte influx and leak plasma proteins into the airway mucosa. These vascular changes are driven by the immune response to the organisms. Plasma leakage results from gaps between endothelial cells, as well as from increased vascular surface area and probably other changes in the newly formed and remodeled blood vessels. Treatment with long-acting beta2 agonists can reduce but not eliminate the plasma occurring after infection. In addition to the elevated baseline leakage, the remodeled vessels in the airway mucosa are abnormally sensitive to substance P, but not to platelet-activating factor or serotonin, suggesting that the infection leads to a selective upregulation of NK1 receptors on the vasculature. The formation of new vessels and the remodeling of existing vessels are likely to be induced by multiple growth factors, including vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang1). VEGF increases vascular permeability, but Ang1 has the opposite effect. This feature is consistent with evidence that VEGF and Ang1 play complementary and coordinated roles in vascular growth and remodeling and have powerful effects on vascular function. Regulation of vascular permeability by VEGF and Ang1 may be their most rapid and potent actions in the adult, as these effects can occur independent of their effects on angiogenesis and vascular remodeling. The ability of Ang1 to block plasma leakage without producing angiogenesis may be therapeutically advantageous. Furthermore, because VEGF and Ang1 have additive effects in promoting angiogenesis but opposite effects on vascular permeability, they could be used together to avoid the formation of leaky vessels in therapeutic angiogenesis. Finally, the elucidation of the protective effect of Ang1 on blood vessel leakiness to plasma proteins raises the possibility of a new strategy for reducing airway edema in inflammatory airway diseases such as asthma and chronic bronchitis.
Disease problems of small rodents, in Quesenberry KE, Carpenter JW (eds): Ferrets, Rabbits , and Rodents
- Donnelly
Donnelly TM: Disease problems of small rodents, in Quesenberry KE, Carpenter JW (eds): Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery (ed 2). St. Louis, MO, Elsevier/Saunders, pp 299-315, 2004
Biology and diseases of rats
- Df Kohn
- Clifford
- Jg Fox
- Lc Anderson
- Fm Loew
- Quimby
Kohn DF, Clifford CB: Biology and diseases of rats, in Fox JG, Anderson LC, Loew FM, Quimby FW (eds): Laboratory Animal Medicine (ed 2). San Diego, CA, Academic Press, pp 121-165, 2002
Impact of experimental genital mycoplasmosis on pregnancy outcome in Sprague-Dawley rats Table 1. Common therapeutic agents used to treat rat respiratory disease Agent Dosage/Route Species/Comments Albuterol
- Da Steiner
- Brown
Steiner DA, Brown MB: Impact of experimental genital mycoplasmosis on pregnancy outcome in Sprague-Dawley rats. Infect Immun 62:633-639, 1993 Table 1. Common therapeutic agents used to treat rat respiratory disease Agent Dosage/Route Species/Comments Albuterol
Mycoplasmal and other bacterial diseases of the respiratory system The Mouse in
- Jr Lindsey
- Gh Cassell
- Davidson
- Hl Foster
- Jd Small
- Fox
Lindsey JR, Cassell GH, Davidson MK: Mycoplasmal and other bacterial diseases of the respiratory system, in Foster HL, Small JD, Fox JG (eds): The Mouse in Biomedical Research (vol 2). New York, NY, Academic Press, pp 21-41, 1982
Detection methods for the identification of rodent viral and mycoplasmal infections Comparison of methods for detection of Mycoplasma pulmonis in experimentally and naturally infected rats
- Lussier
- Mk Davidson
- Jr Lindsey
- Brown
- Mb
Lussier G: Detection methods for the identification of rodent viral and mycoplasmal infections. Lab Anim Sci 41:199-225, 1991 25. Davidson MK, Lindsey JR, Brown MB, et al: Comparison of methods for detection of Mycoplasma pulmonis in experimentally and naturally infected rats. J Clin Microbiol 14:646-655, 1981
Infec-tious Diseases of Mice and Rats
- Lindsey Jr Ga Boorman
- Collings Mj
Lindsey JR, Boorman GA, Collings MJ, et al: Infec-tious Diseases of Mice and Rats. Washington, DC, National Academy Press, 1991
Diseases due to mycoplasmas and rickettsias
- J R Lindsey
- G H Cassell
- H J Baker
Lindsey JR, Cassell GH, Baker HJ: Diseases due to
mycoplasmas and rickettsias, in Benirschke K, Garner FM, Jones TC (eds): Pathology of Laboratory
Animals (vol 2). New York, NY, Springer-Verlag, pp
1481-1550, 1978
Disease problems of small rodents Ferrets, Rabbits , and Rodents: Clinical Medicine and Surgery
- Tm Donnelly
Donnelly TM: Disease problems of small rodents, in
Quesenberry KE, Carpenter JW (eds): Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery (ed
2). St. Louis, MO, Elsevier/Saunders, pp 299-315,
2004
Infectious Diseases of Mice and Rats
- J R Lindsey
- G A Boorman
- M J Collings
Lindsey JR, Boorman GA, Collings MJ, et al: Infectious Diseases of Mice and Rats. Washington, DC,
National Academy Press, 1991
Hoppes S: Rat medicine
Hoppes S: Rat medicine. Proc Assoc Avian Vet, San
Diego, CA, pp 265-275, 2010