1.GM1ガングリオシドーシスモデルマウスヘのヒト正常型β-ガラクトシダーゼトランスジーンの導入と解析

概要

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GM1-gangliosidosis is an inherited neurodegenerative disease caused by a deficiency of lysosomal acid β-galactosidase that catalyzes the terminal nonreducing β-galactosidic residue from a variety of glycoconjugates including ganglioside GM1. We recently generated β-galactosidase knockout (β-Gal KO) mice and characterized them as an authentic model for GM1-gangliosidosis. The β-Gal KO mice present progressive neurological manifestations, widespread cerebral lesions and massive storage of ganglioside GM1 in brains. In this study, we introduced the human β-Gal transgene into β-Gal KO mice in order to rescue their GM1-gangliosidosis phenotypes. The transgenic mice carrying the β-actin promoter/human β-Gal cDNA transgene and overexpressing human β-Gal were mated with the β-Gal KO mice to obtain F1 progeny. By intercrossing F1 mice, we obtained β-Gal KO mice with the human β-Gal transgene. These mice were phenotypically normal and expressed human β-galactosidase at high levels in all tissues examined. They showed no abnormalities in the pathological findings. In addition, we could not detect the excess storage of ganglioside GM1 and asialo GM1 in their brains. These results clearly demonstrate that the human β-galactosidase transgene is expressed in the β-Gal KO mice and the human enzyme can rescue the mouse GM1-gangliosidosis.