title: Beta-galactosidase-deficient mouse as an animal model for GM1-gangliosidosis.
abstract: GM1-gangliosidosis is a progressive neurological disease in humans caused by deficiency of lysosomal acid beta-galactosidase, which hydrolyses the terminal beta-galactosidic residue from ganglioside GM1 and other glycoconjugates. In this study, we generated a mouse model for GM1-gangliosidosis by gene targeting in embryonic stem cells. The mouse homozygous for the disrupted beta-galactosidase gene showed beta-galactosidase deficiency, presented with progressive spastic diplegia, and died of emaciation at 7-10 months of age. Pathologically, PAS-positive intracytoplasmic storage was observed in neuronal cells of various areas in the brain. Biochemical analysis revealed a marked accumulation of ganglioside GM1 and asialo GM1 in brain tissue. This animal model will be useful for pathogenetic analysis and therapeutic trial of human GM1-gangliosidosis.
authors.affiliation: Department of Veterinary Science, National Institute of Health, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Matsuda
authors.forename: O
authors.initials: O
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Oshima
authors.forename: A
authors.initials: A
authors.lastname: Ogura
authors.forename: Y
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Asano
authors.forename: K
authors.initials: K
authors.lastname: Takimoto
authors.forename: K
authors.initials: K
authors.lastname: Sukegawa
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Naiki
mesh_terms: D000818:Animals; D002855:Chromatography, Thin Layer; D004195:Disease Models, Animal; D016537:Gangliosidosis, GM1 / Q000378:metabolism* / Q000473:pathology; D018390:Gene Targeting; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D001616:beta-Galactosidase / Q000172:deficiency / Q000235:genetics*
chemical_list: D001616:beta-Galactosidase