beta-galactosidase-deficient mouse as an animal model for G(M1)-gangliosidosis

G(M1)-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 G(M1) and other glycoconjugates. In this study, we generated a mouse model for G(M1)-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 G(M1) and asialo G(M1) in brain tissue. This animal model will be useful for pathogenetic analysis and therapeutic trial of human G(M1)-gangliosidosis.