No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Genetic reliability of commercially bred laboratory mice
Abstract
An analysis of 20 mouse colonies from 10 different breeders sampled over a period of up to a year using the mandible-analysis technique revealed 3 major cases of lack of authenticity: supply of mice as a pure strain from a colony founded by an unidentified cross: blending of 2 or 3 stocks into a single colony the offspring of which were sold under 3 different names, none of which were authentic; differences between nominally identical stock from 2 sources.
These findings are discussed in relation to previously published information using named strains, and a genetic monitoring scheme for commercial breeders is proposed.
... There is now an urgent need for improved methods of checking the genetic identity ('authenticity') of the many inbred and congenic strains of mice and rats used in biomedical research. In the past, most research workers have taken the authenticity of such strains on trust, but sometimes this trust is misplaced (Festing, 1974; Krog, 1976; Groen, 1977). Moreover, eyen if strains do not become genetically contaminated, errors in labelling when animals are transported could result in research workers inadvertently using the wrong animals. ...
... Skin grafting is sensitive for discovering whether a strain is inbred, but is clumsy as a means of strain identification: it also takes far too long (12-100 days) to get an answer. Mandible shape (Festing, 1974) is a satisfactory method for routine screening, but needs to be backed up by other methods, as it sometimes produces false positive results. Moreover, it is too mathematical in approach for the average biomedical research worker. ...
Strain-specific polyvalent anoantisera may be obtained by injecting lymphocytes pooled from several different strains into an inbred recipient. 6 sera of this type were produced in rats and 23 in mice. A dye-exclusion microcytotoxic test was used to evaluate the strain specificity of such sera. A total of 663 out of 713 (93·0%) of the tests conformed with expectation, but there were 48 (6·7%) false negative results in which the test failed to detect non-authentic animals. There were also 2 (0·3%) false positive results, in which authentic animals were shown as non-authentic. These were attributed to technical errors. Most false negative results occurred when serum and test cell suspensions matched at the major histocompatibility complex.
It was concluded that the use of strain-specific polyvalent immune sera, coupled with a simple immunological test such as the microcytotoxic test, offers a sensitive and quick new method for routine genetic quality control.
... These were incubated overnight in a few ml tap water with a pinch of the proteolytic enzyme papain to clean off the remaining flesh, incisors were removed, and the mandibles were dried and stored in plastic bags. A series of 11 measurements were made as previously described (Festing, 1974 ), and these were used to compute 4 discriminant functions (DFs) describing the shape of the mandible. The coefficients used in calculating the DFs are given inTable 3. ...
... The mean and within-sample standard deviation for each of the 4 DFs was calculated for each sample. However, the standard deviation among sample means from the same colony was taken from a previous study (Festing, 1974) involving a total of 103 samples (Table 1). Sample means were used to calculate an overall mean for the colony or strain and these data were used to construct control charts as used in industrial quality control (Thirkettle, 1968 ). ...
SUMMARY A method of analysing mandible samples using 4 discriminant functions to describe mandible shape, and plotting the samples on control charts, as used in industrial quality control, is described. Repeated samples from 3 different colonies gave consistent results, with only occasional sam- ples 'out of control'. 5 known 'illegitimate' samples were correctly rejected, and 3 out of 4 'legitimate' samples were accepted as belonging to stock LACA. In the 4th case lack of fit was attributed to subline-differentiation. This method of genetic analysis is practical for the large-scale genetic monitoring of laboratory mouse strains and stocks, and a Genetic Monitor- ing Scheme is being offered to commercial breeders. The Accreditation Scheme for breeders of laboratory animals was started in ) 950 with the aim of improving the quality of animals available to bio- medical research workers in the United Kingdom. In 1969 a microbiologicalgrading scheme was introduced in which each accredited colony was screened for the presence of specified pathogenic micro- organisms, and graded according to the findings (Townsend 1969). The need for a method of genetic quality control has already been emphasised (Festing, )974). The development of the 'mandible analysis' technique (Festing, 1972, 1973a, 1973b) in which strains and stocks of laboratory mice can be identified from the shape of their right mandible, has now made it possible to introduce 'genetic monitoring' of mice into the Accreditation Scheme. The genetic monitoring (GM) scheme is a voluntary one, open to all accred- ited breeders of mice and, in the future, other species. It makes provision for the monitoring of inbred strains, outbred stocks and F 1 hybrids. How- ever, breeders wishing to enter the scheme must agree to abide by a number of rules in addition to those required under the microbiological grading scheme (Laboratory Animals Centre, )974). For example, the breeder must satisfy
... Human mistakes and mismanagement, murine size and abilities, and the genetics of coat colors, have all led to the inadvertent mixing of murine genetic material that researchers were attempting to separate and define. In 1974, the importance of genetic monitoring in commercial strains was demonstrated by Festing using mandibular measurements to determine genetic background (Festing, 1974). Roderick et al., in 1971 proposed using isoenzyme alleles to genetically monitor animals. ...
In the early days of research involving mice and rats, the importance of both genetic and health quality and monitoring of that quality was not recognized. The health quality of animals was quickly reflected in sick animals that could not be used for research, so immediate strides were made to ensure animal health in the research environment. Recognition of and efforts to maintain genetic quality lagged behind as laboratory animal genetics was initially only important to geneticists. As detailed investigations into genetics and immunology began, the inbred mouse and more recently, the rat, arose as genetic models of disease (Malakoff, 2000) and with those came the challenge of maintaining genetic homogeneity. Human error and genetic drift are ever-present sources of unwanted genetic heterogeneity, which ultimately lead to experimental irreproducibility. Genetic monitoring and colony maintenance quality control are necessary measures to detect and remove unwanted genetic heterogeneity. This chapter will discuss the rationale for genetic homogeneity and monitoring, the history of genetic monitoring from its inception to today, and current and historical means by which this may be accomplished. Also addressed in the chapter are current monitoring paradigms, or genetic quality control, for mice and rats, including inbred, congenic, outbred, and genetically engineered strains, as well as the role of breeders, vivaria, and end users in genetic quality control. Finally, the future of genetic monitoring and genetic quality control will be discussed.
... Almost in all laboratory animal houses, the breeding colony of outbred stock was founded with minimum number of males and females and was subjected to closed colony mating for more than 45 years at the same institute. In the United Kingdom, Festing [5] reported several cases of deficiency in authenticity of inbred and non-inbred mouse stocks. In India outbred stock are not being monitored for their population genetic structure using molecular markers. ...
Molecular genetic analysis was performed using random amplified polymorphic DNA (RAPD) on three commonly used laboratory bred rodent genera viz. mouse (Mus musculus), rat (Rattus norvegicus) and guinea pig (Cavia porcellus) as sampled from the breeding colony maintained at the Animal Facility, CSIR-Indian Institute of Toxicology Research, Lucknow. In this study, 60 samples, 20 from each genus, were analyzed for evaluation of genetic structure of rodent stocks based on polymorphic bands using RAPD markers. Thirty five random primers were assessed for RAPD analysis. Out of 35, only 20 primers generated a total of 56.88 % polymorphic bands among mice, rats and guinea pigs. The results revealed significantly variant and distinct fingerprint patterns specific to each of the genus. Within-genera analysis, the highest (89.0 %) amount of genetic homogeneity was observed in mice samples and the least (79.3 %) were observed in guinea pig samples. The amount of genetic homogeneity was observed very high within all genera. The average genetic diversity index observed was low (0.045) for mice and high (0.094) for guinea pigs. The inter-generic distances were maximum (0.8775) between mice and guinea pigs; and the minimum (0.5143) between rats and mice. The study proved that the RAPD markers are useful as genetic markers for assessment of genetic structure as well as inter-generic variability assessments.
... In some cases, we found that all was not well. Several of the outbred stocks had become genetically contaminated (13), and, although every inbred strain and each colony of outbred stock had a unique shape to their mandibles, there was no clear distinction between Wistar and Sprague-Dawley rats, because individual colonies within these two stocks differed (14,15). For many years, I was puzzled as to why bone shape is so strongly inherited, although the actual shape of the mandible, and other bones, does not seem to matter very much. ...
Everybody's career depends on many chance factors: the people one meets, the opportunities which are available, or the state of a scientific discipline. Mine is no exception. I started out in agriculture, obtained a PhD in quantitative genetics, and spent most of my career concerned with the use of animals in biomedical research. Soon after I joined the Medical Research Council Laboratory Animals Centre in 1966, as their geneticist in charge of many species and strains of laboratory animals, I was introduced to Russell and Burch's book, The Principles of Humane Experimental Technique. It had a significant effect on my future, which has encompassed two related themes: the need for better experimental design, and the conviction that, in most research, inbred strains of rats and mice should normally be used in preference to genetically undefined outbred stocks. The establishment of the FRAME Reduction Committee has helped me to pursue both of these, although toxicologists continue to ignore basic design principles, by using outbred stocks.
... In some cases, we found that all was not well. Several of the outbred stocks had become genetically contaminated (13), and, although every inbred strain and each colony of outbred stock had a unique shape to their mandibles, there was no clear distinction between Wistar and Sprague-Dawley rats, because individual colonies within these two stocks differed (14,15). For many years, I was puzzled as to why bone shape is so strongly inherited, although the actual shape of the mandible, and other bones, does not seem to matter very much. ...
According to the US Food and Drugs Administration (Food and Drug Administration (2004) Challenge and opportunity on the critical path to new medical products.) “The inability to better assess and predict product safety leads to failures during clinical development and, occasionally, after marketing”. This increases the cost of new drugs as clinical trials are even more expensive than pre-clinical testing.
One relatively easy way of improving toxicity testing is to improve the design of animal experiments. A fundamental principle when designing an experiment is to control all variables except the one of interest: the treatment. Toxicologist and pharmacologists have widely ignored this principle by using genetically heterogeneous “outbred” rats and mice, increasing the chance of false-negative results. By using isogenic (inbred or F1 hybrid, see
Note 1) rats and mice instead of outbred stocks the signal/noise ratio and the power of the experiments can be increased at little extra cost whilst using no more animals. Moreover, the power of the experiment can be further increased by using more than one strain, as this reduces the chance of selecting one which is resistant to the test chemical. This can also be done without increasing the total number of animals by using a factorial experimental design, e.g. if the ten outbred animals per treatment group in a 28-day toxicity test were replaced by two animals of each of five strains (still ten animals per treatment group) selected to be as genetically diverse as possible, this would increase the signal/noise ratio and power of the experiment. This would allow safety to be assessed using the most sensitive strain.
Toxicologists should also consider making more use of the mouse instead of the rat. They are less costly to maintain, use less test substance, there are many inbred and genetically modified strains, and it is easier to identify gene loci controlling variation in response to xenobiotics in this species.
We demonstrate here the advantage of using several inbred strains in two parallel studies of the haematological response to chloramphenicol at six dose levels with CD-1 outbred, or using four inbred strains of mice. Toxicity to the white blood cell lineage was easily detected using the inbred strains but not using the outbred stock, clearly showing the advantage of using the multi-inbred strain approach.
... There is a need for a routine, cheap, sensItive and qualitative test for the authenticity of inbred strains of mice. The mandible-shape technique (Festing, 1974Festing, , 1979), is a sensitive, quantitative technique but it can give false positive results and so needs to be backed up by other methods. The recently devised polyvalent strain-specific alloantisera technique (Festing & Totman, 1980) is qualitative but not yet routinely available. ...
Haemoglobin and glucosephosphate isomerase phenotypes can be determined on a single gel by electrofocusing of haemolysates. It is proposed that the number of phenotypic combinations produced by this procedure makes it suitable for the genetic monitoring of the more commonly used inbred strains of mice.
The role of mandibular phenotype in the development of Class III malocclusion remains unclear. The purpose of this study was to determine whether the form of the mandible differed between prepubertal individuals with Class I and Class III malocclusions. Lateral cephalographs of 73 children of European-American descent aged between 5-11 years with Class III malocclusion were compared to those of 60 counterparts with a normal, Class I molar occlusion. The cephalographs were traced and checked, and eight homologous mandibular landmarks were digitized. Average mandibular geometries, scaled to an equivalent size, were generated using Procrustes superimposition. Euclidean distance matrix analysis (EDMA) was undertaken to corroborate the Procrustes analysis, and bivariate analysis utilizing eight linear and five angular measurements was also performed. Residuals and F-values from Procrustes analysis indicated that mandibular configurations differed statistically for Class I and Class III types. EDMA confirmed that the Class I and Class III geometries were significantly different, revealing that the greatest differences in morphology arose in the anterior-most mandibular regions. As well, most variables showed statistically significant differences when the Class I and Class III mandibular types were compared. When the sample was subdivided into seven age- and sex-matched groups, nearly all age-based comparisons were significantly different. It is concluded that the morphology of the mandible differs in individuals with Class III malocclusions when compared to the normal Class I configuration, and that these alterations may indicate dichotomous postnatal mandibular ontogeny.
Genetic monitoring is an essential component of colony management and for the rat has been accomplished primarily by using immunological and biochemical markers. Here, we report that simple sequence length polymorphisms (SSLPs) are a faster and more economical way of monitoring inbred strains of rats. We characterized 61 inbred strains of rats, using primer pairs for 37 SSLPs. Each of these loci appeared to be highly polymorphic, with the number of alleles per locus ranging between 3 and 14 and, as a result, all the 61 inbred strains tested in this study could be provided with a unique strain profile. These strain profiles are also used for estimating the degree of similarity between strains. This information may provide the rationale in selecting strains for genetic crosses or for other specific purposes.
The aim of this survey was to measure levels of genetic variation within and between 5 different strains of outbred Swiss mice. Ten to 15 animals from each strain (NIH, Q(S), ARC, IMVS and STUD) were typed, using allozyme electrophoresis, at 10 gene loci: Mod-1, Idh-1, Gpi-I, Es-1, Es-3, Hbb, Pep-3, Gr-1, Got-2 and Pgm-1. Polymorphic variation in at least one of the 5 strains was detected at all 10 loci. The proportion of polymorphic loci ranged from 0.3 (NIH) to 0.8 (IMVS) with a mean of 0.52. Average expected heterozygosities ranged from 0.08 (NIH) to 0.37 (IMVS) with a mean of 0.21. The inbred strain SWR was, as expected, homozygous at all 10 loci. The amount of allelic substitution between pairs of strains was quantified using Nei's genetic distance, and a dendrogram based on these genetic distances showed a close overall similarity in its branching pattern to the known genealogy of the strains. This survey showed that a considerable degree of genetic variation persists in the 5 strains examined, a level of variation similar to that previously detected by Rice and O'Brien (1980) in 3 other outbred Swiss strains.
Because of the similarity of their allelic profiles it was assumed that 'ICR' non-inbred mouse colonies were of common origin: however there were differences in allelic frequencies between them. It was also found that the allelic frequency a the C3-1 locus differed between samples from the same colony. Research workers should therefore be aware that the genetic variability of outbred animals may vary among samples, even if the animals are properly designated and supplied from the same breeder.
The extent of allelic variation has been estimated at 46 structural gene loci within three major colonies of Swiss mice and between inbred derivative strains. The colonies have retained nearly the same amount and type of variation found in natural murine or human populations despite laboratory propagation for more than 50 years (175 generations). The population genetic structures of the Swiss mouse colonies were comparable to an island population in which random fixation, and not inbreeding or population bottlenecks, is apparently responsible for slight losses in genetic variance.
10 inbred strains of mice including NOD and NON were identified by discriminant and canonical discriminant analysis of the mandible measurements. The number of erroneous discriminations was 0·5% (1/199) for the females and 0% for males (0/232). In canonical discriminant analysis (discriminant analysis with reduction of dimensionality), NOD and NON inbred strains were separately located on 2-dimensional planes, Z 1 -Z 2 , Z 1 -Z 3 , and Z 2 -Z 3 .
These results clearly indicate that the genetic constitution of NOD and NON differs, although they have been established from a common ancestor ICR mouse. Causes of divergence between NOD and NON mice arc discussed.
The methodology of genetics may help in the study of many kinds of phenotypes. This chapter describes the genetic variables available to geneticists, the possible genotypes of experimental animals, and their use. The protein structures appearing as a result of gene effects may play various roles in the development of the phenotype. The neurochemical reactions represent only a part of the biochemical reaction complex maintaining the whole organism. Application of the concepts to the relationship between the phenotype and the genotype makes it clear that the individual phenotypes can only rarely be found to be influenced by the effect of a single major gene. The methods presented in the chapter are mainly those of traditional vertebrate genetics. Methods used in invertebrates have been touched upon only in some cases. Several methods that go beyond the bounds of the organism have also undergone remarkable development. Excellent genetic studies can be made using somatic cell cultures and cell hybrids.
Inbred mice of the strains C57B1/6, CBA, C3H, Balb/c and DBA/2 from a total of 17 different sources within Australia were compared, utilizing 12 different blood proteins and a morphometric analysis of a series of lower jaws. Evidence for genetic differentiation between sublines was found in only two cases. Evidence for the recent contamination of an inbred strain with another stock was found in one case.
The case for evaluating the safety of drugs by using several inbred strains of a laboratory animal species arranged in a factorial design of experiment rather than a single outbred stock is discussed. It is concluded that the factorial design should give a more powerful experiment, produce more information and have a more valid basis for extrapolation to man. This extra information will be obtained at the expense of a more complex statistical analysis and will present some practical problems in obtaining a supply of several different inbred strains, although the total size of the experiment should not increase. It is shown that the differences between inbred strains may be a valuable aid in interpreting the results of toxicity tests.
The major symptom of Alzheimer’s disease is dementia progressing with age. Its clinical diagnosis is preceded by a long prodromal period of brain pathology that encompasses both formation of extracellular amyloid and intraneuronal tau deposits in the brain and widespread neuronal death. At present, familial cases of dementia provide the most promising foundation for modeling neurodegenerative tauopathies, a group of heterogeneous disorders characterized by prominent intracellular accumulation of hyperphosphorylated tau protein. In this chapter, we describe major behavioral hallmarks of tauopathies, briefly outline the genetics underlying familial cases, and discuss the arising implications for modeling the disease in transgenic mouse systems. The selection of tests performed to evaluate the phenotype of a model should be guided by the key behavioral hallmarks that characterize human disorder and their homology to mouse cognitive systems. We attempt to provide general guidelines and establish criteria for modeling dementia in a mouse; however, interpretations of obtained results should avoid a reductionist “one gene, one disease” explanation of model characteristics. Rather, the focus should be directed to the question of how the mouse genome can cope with the over-expression of the protein coded by transgene(s). While each model is valuable within its own constraints and the experiments performed are guided by specific hypotheses, we seek to expand upon their methodology by offering guidance spanning from issues of mouse husbandry to choices of behavioral tests and routes of drug administration that might increase the external validity of studies and consequently optimize the translational aspect of preclinical research.
The laboratory animal can be thought of as the toxicologist's major instrument for use in a safety evaluation programme. Consequently, to obtain reliable results from such an ‘instrument’, the toxicologist must obtain animals of the highest quality available, and maintain as well as monitor them in such a manner that intercurrent infections or latent diseases do not produce effects leading to erroneous conclusions. The procedures described will enhance the reliability of the results obtained in toxicological studies.
Genetically uniform or isogenic strains (inbred strains and F1 hybrids) have a number of properties that make them valuable in toxicity testing, provided the experimental design can be modified to include more than one such strain. Isogenicity and homozygosity lead to great phenotypic uniformity, high long-term genetic stability, high identifiability, large differences between strains (individuality), and the possibility of setting up daughter colonies genetically identical to the parents. This in turn means that many isogenic strains are internationally distributed, and that considerable background data exist on the characteristics of the common strains. Toxicity testing usually involves the calculation of dose-response curves. Use of phenotypically variable nonisogenic stocks reduces the precision with which such curves can be estimated, without many other benefits. A single isogenic strain may not be satisfactory as it may be resistant to the drug being tested. However, the use of several isogenic strains with a factorial experimental design would overcome this problem, would give high statistical precision, and would provide a better basis for extrapolation to humans than the use of a single stock. Such a design would make it possible to choose a range of strains on the basis of known drug sensitivities, it would be highly repeatable, it would allow comparison of different drugs, and it would show whether the response was genetically determined. The benefits of such an experimental design far outweigh the disadvantages, which are mostly of a practical nature.
Evidence for and against the possibility that the autoimmune disease of NZB mice has a viral aetiology is presented. It is considered that the case for a viral aetiology is unproven, although the possibility exists that virus may be present in incomplete form. Widely varying experimental results can be expected in experiments involving NZB mice until acceptable standards of mouse strain definition are laid down. Thus the comparison of results obtained from studies of NZB mice of diverse origin may invite misleading conclusions.
The major symptom of Alzheimer’s disease is rapidly progressing dementia, coinciding with the formation of amyloid and tau deposits in the central nervous system, and neuronal death. At present familial cases of dementias provide the most promising foundation for modelling neurodegeneration. We describe the mnemonic and other major behavioral symptoms of tauopathies, briefly outline the genetics underlying familiar cases and discuss the arising implications for modelling the disease in mostly transgenic mouse lines. We then depict to what degree the most recent mouse models replicate pathological and cognitive characteristics observed in patients.
There is no universally valid behavioral test battery to evaluate mouse models. The selection of individual tests depends on the behavioral and/or memory system in focus, the type of a model and how well it replicates the pathology of a disease and the amount of control over the genetic background of the mouse model. However it is possible to provide guidelines and criteria for modelling the neurodegeneration, setting up the experiments and choosing relevant tests. One should not adopt a “one (trans)gene, one disease” interpretation, but should try to understand how the mouse genome copes with the protein expression of the transgene in question. Further, it is not possible to recommend some mouse models over others since each model is valuable within its own constraints, and the way experiments are performed often reflects the idiosyncratic reality of specific laboratories. Our purpose is to improve bridging molecular and behavioural approaches in translational research.
The relationship between morphometric and structural gene variation was examined in a group of 15 inbred mouse strains. The genetic distance of Nei was calculated between each of the strains based upon 36-78 biochemical loci. Mahalanobis distances based on 11 mandibular measurements were computed between the strains as well. The correlation coefficient between genetic distance and metric distance was low (r = 0.24 ± 0.1). Genetic distance was highly correlated with elapsed time of divergence of the strains (r = 0.73 ± 0.15) while morphometric distance, though clearly heritable, was not significantly correlated with elapsed time. These results indicate that morphological change and biochemical change are poorly coupled in these strains and suggest that the cumulative differences in structural gene mutations may provide a more accurate measure of phylogenetic relationships between biological groups than do measures of morphological distance (such as mandibular characters) based upon multivariate analysis.
Multivariate analysis of mandible measurements was applied to identify and to investigate the genetic relationships between 5 outbred stocks of female mice, Dlv:CD-1, Hg:CD-1, Crj:CD-1, CF-1 and Slc:ddY. (1) Principal component analysis revealed that CF-1 had a relatively large mandible with an obtuse muscular process and a low anterior mandibular body, whereas Hg:CD-1 had a smaller mandible and exhibited intermediate values in terms of muscular process shape and anterior height. Crj:CD-1 showed a moderately large mandible and a higher anterior mandibular body. While the mandibles of Dlv:CD-1 and Slc:ddY were comparatively similar to each other in that they were both medium-sized, the former had an acute muscular process projecting posteriorly whereas the latter had a less prominent process. These morphological relationships between the 5 stocks determined by principal component analysis were generally in agreement with Mahalanobis' distance between stocks based on the same mandible measurements. (2) According to the results of discriminant analysis, the frequency of misclassification was 11.4%, or 9/79 head when actual mandible measurements were used in categorization and 10.1%, or 8/79, when relative values, which exclude the size effect, were used. These data indicate that the genetic constitution of the 3 CD-1 stocks examined in this study differed from one another. (3) Based on dendrograms calculated from actual mandible measurements and relative values, Dlv:CD-1 was more closely related to CF-1 or Slc:ddY, which are derived from mice of other origins, than the CD-1 stocks examined in this study. Thus genetic monitoring seems to be essential for outbred stocks as well as for inbred strains.
A good reproducibility of the experimentations in animals allows a better appreciation of immunogenicity of vaccine candidates. Standardized methods of administration, samplings and analyses ensure for one part to the expected consistency. However, laboratory animals by themselves contribute to variability. The question was raised whether different strains or a same strain originating from different breeders would significantly influence immunogenicity results. Indeed, different animal suppliers might be needed in case of some supply shortage or sudden increase in laboratory needs. To this aim, antibody responses were assessed through several animal experimentation protocols designed to evaluate the immunogenicity of vaccine candidates against AIDS. Protocols included intramuscular immunizations of guinea-pigs with HIV-1 antigens expressed by a canarypox virus vector, the ALVAC-HIV (vCP205) virus, or by recombinant proteins such as toxoïd TatIIIB or gp160 MN/LAI-2. The latter antigen was also administrated by nasal route to mice. According to the immunization protocol, total and TatIIIB or gp160 MN/LAI-2 specific IgG and IgA antibodies were measured by ELISA at different time-points, in sera from all animals, and in nasal and vaginal secretions from mice immunized by the nasal route. The results showed that, in the mouse species, responses were very different between strains, and also, for a given strain, between mice from different breeders. The variability was confirmed with the guinea-pig species. Without calling into question the predicibility of the animal models, to estimate the immunogenicity of a vaccine candidate, and to assess a better homogeneity of the results all along the study of the new antigen, it is advisable to keep the same species and animal strain and to ask for the animals to the same breeding center.
Morphospatial disharmony of the craniomaxillary and mandibular complexes may yield apparent mandibular prognathism, but Class III malocclusions can exist with any number of aberrations of the craniofacial complex. Deficient orthocephalization of the cranial base allied with a smaller anterior cranial base component has been implicated in the etiology of Class III malocclusions. Whereas the more acute cranial base angle may affect the articulation of the condyles resulting in their forward displacement, the reduction in anterior cranial size may affect the position of the maxilla. As well, intrinsic skeletal elements of the maxillary complex may be responsible for maxillary hypoplasia that may exacerbate the anterior crossbite seen in the Class III condition. Conversely, with an orthognathic maxilla, condylar hyperplasia and anterior positioning of the condyles at the temporo-mandibular joint may produce an anterior crossbite. Aside from the skeletal components, soft tissue matrices, particularly labial pressure from the circumoral musculature, may influence the final outcome of craniofacial growth of a child skeletally predisposed to Class III conditions. Indeed, as some Asian ethnic groups demonstrate an increased prevalence of Class III malocclusions, it is likely that the skeletal components and soft tissues matrices are genetically determined. Presumably, the co-morphologies of the craniomaxillary and mandibular complexes are likely dependent upon candidate genes that undergo gene-environmental interactions to yield Class III malocclusions. The identification of such genes is a desirable step in unraveling the complexity of Class III malocclusions. With this knowledge, the clinician may elect an early course of dentofacial orthopedic and orthodontic treatments aimed at preventing the development of Class III malocclusions.
Rules for designating inbred strains of mice are presented, along with a list of strains with their origins and characteristics, a table of biochemical polymorphisms, and standard subline designations. The Committee recommends the use of the following abbreviations for the names of inbred strains in compound symbols and in other situations where brevity is desired. In all cases, the full strain designations should always be given in either the Materials and Methods or Introduction section of any paper; e.g., 'AKR/K x DBA/2J F1 (hereafter called AKD2F1)'; in hybrid designations, the female parent should be listed first. Strain:Abbreviation; AKR:AK; BALB/c:C; C3H:C3; C57BL:B; C57BL/6:B6; C57BL/10:B10; C57BR:BR; C57L:L; DBA/1:D1; DBA/2:D2; HRS/J:HR; RIII:R3.
INBRED strains of mice have been widely used since 1909, and more than 200 distinct strains or sub-strains are now recognized2. In practice, however, although each strain has a unique set of characteristics such as mean life-span, tumour incidence, behaviour, reproductive performance and blood group, different strains may be morphologically indistinguishable. Thus, for example, several of the widely used inbred albino strains cannot easily be told apart from the more common albino randomly bred strains. Unfortunately, although simplified biochemical methods for strain identification have been developed3, they are still too costly and laborious.
The shape of the mandible in. nine sublines of C57BL/Gr, seven other strains of ‘C57 ancestry’ and four unrelated strains was studied by multivariate techniques. The generalized distance function was used to classify individuals in the groups which they most closely resembled. The degree of misclassification depended on the pedigree relationship between strains and sublines. The generalized distance between pairs of subline centeroids was also highly correlated (r = 0·60) with the number of generations between them. A canonical variate analysis was used to reduce the dimensionality so that a graphical display of the relationships between strains and sublines could be made. The results agreed closely with the classification analysis. It was concluded that the shape of the mandible could be used for subline identification though the accuracy of this technique depends on how closely the sublines are related.
Data are presented on the life span and pathology of 15 inbred and 2 outbred strains of mice, and 1 inbred and 1 outbred strain of rats, maintained under specified-pathogen-free (SPF) conditions. Among the mice, longevity ranged from 312 to 802 days. Survival curves for each strain are given. Neoplasia was the most common pathological finding.
Biology of the laboratory mouse The grading of commercially-bred Record 85,225. analysis of subline divergence in the shape of the by mandible analysis Cancer laboratory animals
- E L Green
- G T Townsend
Green, E. L. (1966). Biology of the laboratory mouse, 2nd ed. New York: Staats, J. (1972). Standardizednomenclature Research 32,1609. Townsend, G. T. (1969). The grading of commercially-bred Record 85,225. analysis of subline divergence in the shape of the by mandible analysis. In The laboratory Fischer. (MRC McGraw-HilI. for inbred strains of mice, 5th listing. Cancer laboratory animals.Veterinary