Double KO Mice of β-1,4-N-acetylgalactosaminyltransferase (GM2/GD2 Synthase) and α-2,8-sialyltransferase (GD3 Synthase)

Abstract

Gangliosides have been considered to play important roles in the development and differentiation of nervous systems in vertebrates. They have been also considered to have neurotrophic activity. In order to directly address these biological functions, we generated knockout mice of β-1,4-N-acetylgalactosaminyltransferase gene (Takamiya et al. 1996) that is responsible for the synthesis of GM2 and GD2 (and GA2), and those of α-2,8-sialyltransferase gene (Okada et al. 2000) that is responsible for the synthesis of GD3. These KO mice showed relatively mild abnormal phenotypes than expected. This seemed due to the compensatory effects of the remaining glycolipids in the individual KO mice (Furukawa et al. 2004). Therefore, we mated these two KO mice in order to generate double KO mice in which only GM3 should remain. Now we can largely eliminate the compensatory effects of remaining glycolipids and correctly observe the effects of ganglioside deficiency. DKO mutants were born with almost normal appearance, and grew up for a while after birth. However, they demonstrated marked neurodegeneration from early stages of life, and various abnormal phenotypes probably caused by neurodegeneration (Inoue et al. 2002).