KO Mice of β1,4-N-acetylgalactosaminyltransferase (GM2/GD2 Synthase)
Complex gangliosides have been considered to play important roles in the development and differentiation of nervous systems in vertebrates. In order to directly address this issue, we generated knockout mice of beta 1,4-N-acetylgalactosaminyltransferase gene (Nagata et al. 1992) that is responsible for the synthesis of GM2 and GD2 (and GA2), and clearly showed that this enzyme is really critical for the synthesis of all complex gangliosides (Takamiya et al. 1996). Although the null mutant mice showed minor neurological disorders, their brain and nervous tissues were almost normally generated. In contrast, they showed aspermatogenesis (Takamiya et al. 1998) and immuno-dysfunctions. However, the null mutants demonstrated neurodegeneration with aging suggesting roles of complex gangliosides in the maintenance of integrity of nervous systems (Sugiura et al. 2005).
KeywordsTarget Vector Purkinje Neuron Chimeric Mouse Null Mutant Mouse Complex Ganglioside
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- Takamiya K, Yamamoto A, Furukawa K, Yamashiro S, Shin M, Okada M, Fukumoto S, Haraguchi M, Takeda N, Fujimura K, Sakae M, Kishikawa M, Shiku H, Furukawa K, Aizawa S (1996) Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides, but exhibit only subtle defects in their nervous system. Proc Natl Acad Sci USA 93:10662–10667PubMedCrossRefGoogle Scholar
- Takamiya K, Yamamoto A, Zhao J, Furukawa K, Yamashiro S, Okada M, Haraguchi M, Shin M, Takeda N, Kishikawa M, Shiku H, Aizawa S, Furukawa K (1998) Complex gangliosides are essential in spermatogenesis of mice: possible roles in the transport of testosterone. Proc Natl Acad Sci USA 95:12147–12152PubMedCrossRefGoogle Scholar