title: Spontaneous appearance of Tay-Sachs disease in an animal model.
abstract: Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of beta-hexosaminidase A (Hex A). Deficiency of Hex A in TSD is caused by a defect of the alpha-subunit resulting from mutations of the HEXA gene. To date, there is no effective treatment for TSD. Animal models of genetic diseases, similar to those known to exist in humans, are valuable and essential research tools for the study of potentially effective therapies. However, there is no ideal animal model of TSD available for use in therapeutic trials. In the present study, we report an animal model (American flamingo; Phoenicopterus ruber) of TSD with Hex A deficiency occurring spontaneously in nature, with accumulation of G(M2)-ganglioside, deficiency of Hex A enzymatic activity, and a homozygous P469L mutation in exon 12 of the hexa gene. In addition, we have isolated the full-length cDNA sequence of the flamingo, which consists of 1581 nucleotides encoding a protein of 527 amino acids. Its coding sequence indicates approximately 71% identity at the nucleotide level and about 72.5% identity at the amino acid level with the encoding region of the human HEXA gene. This animal model, with many of the same features as TSD in humans, could represent a valuable resource for investigating therapy of TSD.
authors.affiliation: Department of Neurology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Zeng
authors.forename: P A
authors.initials: PA
authors.lastname: Torres
authors.forename: T C
authors.initials: TC
authors.lastname: Viner
authors.forename: Z H
authors.initials: ZH
authors.lastname: Wang
authors.forename: S S
authors.initials: SS
authors.lastname: Raghavan
authors.forename: J
authors.initials: J
authors.lastname: Alroy
authors.forename: G M
authors.initials: GM
authors.lastname: Pastores
authors.forename: E H
authors.initials: EH
authors.lastname: Kolodny
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D001717:Birds / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D054818:Hexosaminidase A / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D009154:Mutation; D013661:Tay-Sachs Disease / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D030161:Avian Proteins; D054818:Hexosaminidase A