Neurovisceral and skeletal GM1 gangliosidosis in dogs with β-galactosidase deficiency

Tufts University, Бостон, Georgia, United States
Science (Impact Factor: 33.61). 09/1985; 229(4712):470-2. DOI: 10.1126/science.3925555
Source: PubMed


Beta-galactosidase-deficient siblings in two litters of English springer spaniel puppies showed a progressive neurological
impairment, dwarfism, orbital hypertelorism, and dysostosis multiplex. An excess of GM1-ganglioside was found in the brain.
Three abnormal oligosaccharides were present in samples of urine, brain, liver, and cartilage. Light microscopy of selected
tissue specimens revealed cytoplasmic vacuoles in neurons, circulating blood cells, macrophages, and chondrocytes. Ultrastructural
studies demonstrated that these membrane-bound vacuoles were of two types--one containing lamellated membranes and the other,
finely granular material. These clinical and pathological findings are similar to those observed in human patients affected
by the infantile form of GM1-gangliosidosis.

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    • "The frequency of carriers in a population substantially exceeds the incidence of the disease; therefore, the presence of carriers makes recessive diseases the most difficult to control in pure-breed animals [11,12]. Canine GM1 gangliosidosis has been reported in other pure-breed dogs including English Springer Spaniels [13], Portuguese Water Dogs [14], and Alaskan Huskies [15]; however, to the best of our knowledge, a large-scale molecular epidemiological survey has not been performed to establish effective measures for the control and prevention of the disease. "
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    ABSTRACT: Canine GM1 gangliosidosis is a fatal disease in the Shiba Inu breed, which is one of the most popular traditional breeds in Japan and is maintained as a standard breed in many countries. Therefore, it is important to control and reduce the prevalence of GM1 gangliosidosis for maintaining the quality of this breed and to ensure supply of healthy dogs to prospective breeders and owners. This molecular epidemiological survey was performed to formulate an effective strategy for the control and prevention of this disease. The survey was carried out among 590 clinically unaffected Shiba Inu dogs from the 8 districts of Japan, and a genotyping test was used to determine nation-wide and regional carrier frequencies. The number and native district of affected dogs identified in 16 years from 1997 to April 2013 were also surveyed retrospectively. Of the 590 dogs examined, 6 dogs (1.02%, 6/590) were carriers: 3 dogs (2.27%, 3/132) from the Kinki district and the other 3 dogs from the Hokkaido, Kanto, and Shikoku districts. The retrospective survey revealed 23 affected dogs, among which, 19 dogs (82.6%) were born within the last 7 years. Of the 23 affected dogs, 12 dogs (52.2%) were from the Kinki district. Pedigree analysis demonstrated that all the affected dogs and carriers with the pedigree information have a close blood relationship. Our results showed that the current carrier frequency for GM1 gangliosidosis is on the average 1.02% in Japan and rather high in the Kinki district, which may be related to the high prevalence observed over the past 16 years in this region. This observation suggests that carrier dogs are distributed all over Japan; however, kennels in the Kinki district may face an increased risk of GM1 gangliosidosis. Therefore, for effective control and prevention of this disease, it is necessary to examine as many breeding dogs as possible from all regions of Japan, especially from kennels located in areas with high prevalence and carrier frequency.
    Full-text · Article · Jul 2013 · BMC Veterinary Research
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    • "In animals, GM1 gangliosidosis has been reported in dogs, cats, calves, and sheep. In dogs, the disease has been detected in mixed-breed beagles [3], English Springer Spaniels (ESSs) [4], Portuguese water dogs (PWDs) [5], Alaskan huskies [6], Shiba Inu dogs (SIDs) [7], and a mixed-breed dog [8]. The molecular defects that cause the disease have been identified in PWDs [9], Alaskan huskies [10], and SIDs [11]. "
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    ABSTRACT: GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of β-galactosidase activity. Effective therapies need to be developed to treat the disease. In Shiba Inu dogs, one of the canine GM1 gangliosidosis models, neurological signs of the disease, including ataxia, start at approximately 5 months of age and progress until the terminal stage at 12 to 15 months of age. In the present study, serial MR images were taken of an affected dog from a model colony of GM1 gangliosidosis and 4 sporadic clinical cases demonstrating the same mutation in order to characterize the MRI features of this canine GM1 gangliosidosis. By 2 months of age at the latest and persisting until the terminal stage of the disease, the MR findings consistently displayed diffuse hyperintensity in the white matter of the entire cerebrum on T2-weighted images. In addition, brain atrophy manifested at 9 months of age and progressed thereafter. Although a definitive diagnosis depends on biochemical and genetic analyses, these MR characteristics could serve as a diagnostic marker in suspect animals with or without neurological signs. Furthermore, serial changes in MR images could be used as a biomarker to noninvasively monitor the efficacy of newly developed therapeutic strategies.
    Full-text · Article · Mar 2012 · The Scientific World Journal
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    • "Similarly, neural stem cells isolated from adult human olfactory bulb biopsies contained self-renewing, multipotential neural stem cells as evidenced by clonal analysis (Pagano et al., 2000). Many neurologic diseases that may potentially benefit from NPC transplantation occur in the dog (Griffiths et al., 1981; Haskins et al., 1984; Alroy et al., 1985; Koppang, 1988; Fischer et al., 1998; Wenger et al., 1999). We recently found that defects in canine NPCs occur in a model of a lysosomal storage disease (Walton and Wolfe, 2007). "
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    ABSTRACT: The dog serves as a large animal model for multiple neurologic diseases that may potentially benefit from neural progenitor cell (NPC) transplantation. In the adult brain, multipotent NPCs reside in the subventricular zone and its rostral and caudal extensions into the olfactory bulb and hippocampus. The olfactory bulb represents a surgically accessible site for obtaining cells for autologous NPC transplantation. To model conditions that would occur for ex vivo gene therapy in the postnatal brain, NPCs were isolated from the canine olfactory bulb, expanded ex vivo under different culture conditions, and compared quantitatively for growth and immunophenotype. Under standard growth conditions, canine olfactory bulb-derived NPCs (OB-cNPCs) could be expanded nearly 500-fold in the time evaluated. Canine OB-cNPCs grown on poly-d-lysine (PDL) or on PDL-fibronectin had similar growth rates, whereas supplementation with leukemia inhibitory factor (LIF) resulted in significantly slower growth. However, when OB-cNPC cultures were grown on PDL-fibronectin or PDL supplemented with LIF, a greater proportion of cells with neuronal markers were generated upon differentiation.
    Preview · Article · Apr 2008 · Journal of Neuroscience Methods
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