An inversion of 25 base pairs causes feline G M2 gangliosidosis variant 0

Martin, Douglas R.; Krum, Barbara K.; Varadarajan, G. S.; Hathcock, Terri; Smith, B. F.; Baker, Henry J.

doi:10.1016/j.expneurol.2004.01.008

Cited by 56 publications

(40 citation statements)

References 34 publications

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“…SD and GM1 cats were obtained from the Baker colony at Auburn University, AL, and result from naturally occurring mutations as previously described (33)(34)(35)(36)(37)(38). SD cats had <3% normal hexosaminidase activity in the cerebral cortex ( 39 ).…”

Section: Catsmentioning

confidence: 99%

Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses

Akgoc

Sena‐Esteves

Martin

et al. 2015

Journal of Lipid Research

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Bis(monoacylglycero)phosphate (BMP) is a negatively charged glycerophospholipid with an unusual sn-1;sn-1\u27 structural configuration. BMP is primarily enriched in endosomal/lysosomal membranes. BMP is thought to play a role in glycosphingolipid degradation and cholesterol transport. Elevated BMP levels have been found in many lysosomal storage diseases (LSDs), suggesting an association with lysosomal storage material. The gangliosidoses are a group of neurodegenerative LSDs involving the accumulation of either GM1 or GM2 gangliosides resulting from inherited deficiencies in beta-galactosidase or beta-hexosaminidase, respectively. Little information is available on BMP levels in gangliosidosis brain tissue. Our results showed that the content of BMP in brain was significantly greater in humans and in animals (mice, cats, American black bears) with either GM1 or GM2 ganglioside storage diseases, than in brains of normal subjects. The storage of BMP and ganglioside GM2 in brain were reduced similarly following adeno-associated viral-mediated gene therapy in Sandhoff disease mice. We also found that C22:6, C18:0, and C18:1 were the predominant BMP fatty acid species in gangliosidosis brains. The results show that BMP accumulates as a secondary storage material in the brain of a broad range of mammals with gangliosidoses

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Section: Catsmentioning

confidence: 99%

Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses

Akgoc

Sena‐Esteves

Martin

et al. 2015

Journal of Lipid Research

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“…5 In domestic animals, naturally occurring Sandhoff-like disease has been reported in only 2 canine breeds (i.e., a Golden Retriever 18 and toy Poodles 16 ) and 4 feline breeds or families (i.e., domestic cats in the United States, 4 Korat cats, 13 Japanese domestic cats, 19 and European Burmese cats 3 ). At present, the pathogenic mutations in all 4 feline families have been identified, 3,8,11,12 but not in canine breeds. The mutation in Japanese domestic cats is a single nucleotide substitution from cytosine to thymine at nucleotide position 667 (c.667C.T) in the open reading frame (ORF) of the feline HEXB gene.…”

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confidence: 99%

Rapid and Simple Polymerase Chain Reaction—Based Diagnostic Assays for GM2 Gangliosidosis Variant 0 (Sandhoff-Like Disease) in Japanese Domestic Cats

et al. 2011

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Abstract. Polymerase chain reaction (PCR)-based assays combined with microchip electrophoresis were developed and evaluated for diagnosis and genotyping of GM2 gangliosidosis variant 0 (Sandhoff-like disease) in Japanese domestic cats. A preliminary genotyping survey was carried out in the population of Japanese domestic cats (1,015 cats in total) in southern Japan. Three kinds of assays including PCR primer-induced restriction analysis (PIRA) and mutagenically separated (MS)-PCR were carried out using blood-stained Flinders Technology Associates filter papers (FTA cards) as templates. The PCR products were analyzed by both agarose gel and microchip electrophoreses. All assays were sufficient to determine the genotypes of this disease, but MS-PCR offered the most rapid and simplest test, as it does not need the restriction enzyme step required in PCR-PIRA. The use of microchip electrophoresis in combination with FTA cards for sampling could shorten the time required for genotyping and simplify the procedure as well. The genotyping survey in the current study did not find any cats that possessed the mutant allele, suggesting that the prevalence of this allele is low (,0.1%) in southern Japan.

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“…Sequence analysis determined that the causative mutation in this domestic shorthair SD cat resulted from a 25-base-pair inversion at the 3' end of the Hexb gene (16). Affected cats have < 3% normal hexosaminidase activity in cerebral cortex and therefore represent an authentic model to study Sandhoff disease.…”

Section: Catsmentioning

confidence: 99%

“…The brain weight of the mouse is around 0.4 grams while an infantile human brain weighs around 400 grams, representing a 1000-fold difference in size (13)(14)(15). A naturally occurring, authentic model of SD in cats (fG M2 Baker) has been previously characterized and could potentially serve as an intermediate model between mouse and man (16)(17)(18)(19). Although the feline brain is closer in size and complexity to the human brain, it is not clear how the mouse and the cat animal models of SD compare to the human patient.…”

Section: Introductionmentioning

confidence: 99%

126. Comparative Analysis of brain lipids in Mice, Cats, and Humans with Sandhoff disease

Seyfried

Baek

Martin

et al. 2009

Molecular Genetics and Metabolism

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Sandhoff disease (SD) is a glycosphingolipid (GSL) storage disease that arises from an autosomal recessive mutation in the gene for the β-subunit of β-Hexosaminidase A (Hexb gene), which catabolizes ganglioside GM2 within lysosomes. Accumulation of GM2 and asialo-GM2 (GA2) occurs primarily in the CNS, leading to neurodegeneration and brain dysfunction. We analyzed the total lipids in the brains of SD mice, cats, and humans. GM2 and GA2 were mostly undetectable in the normal mouse, cat, and human brain. The lipid abnormalities in the SD cat brain were generally intermediate to those observed in the SD mouse and the SD human brains. GM2 comprised 38%, 67%, and 87% of the total brain ganglioside distribution in the SD mice, cats, and humans, respectively. The ratio of GA2 to GM2 was 0.93, 0.13, and 0.27 in the SD mice, cats, and humans, respectively, suggesting that the relative storage of GA2 is greater in the SD mouse than in the SD cat or human. Finally, the myelin-enriched lipids, cerebrosides and sulfatides, were significantly lower in the SD brains than in the control brains. This study is the first comparative analysis of brain lipids in mice, cats, and humans with SD and will be important for designing therapies for Sandhoff disease patients.

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An inversion of 25 base pairs causes feline G M2 gangliosidosis variant 0

Cited by 56 publications

References 34 publications

Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses

Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses

Rapid and Simple Polymerase Chain Reaction—Based Diagnostic Assays for GM2 Gangliosidosis Variant 0 (Sandhoff-Like Disease) in Japanese Domestic Cats

126. Comparative Analysis of brain lipids in Mice, Cats, and Humans with Sandhoff disease

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