Deletion of sialidase NEU3 causes progressive neurodegeneration in Tay-Sachs mice

Abstract

Tay-Sachs disease is a severe lysosomal disorder caused by mutations in the HEXA gene coding for α subunit of lysosomal βhexosaminidase A which converts GM2 to GM3 ganglioside. HexA-/-mice, depleted of β-hexosaminidase A gene, remains asymptomatic to 1 year of age, owing to the ability of these mice to catabolise stored GM2 ganglioside via sialidase(s) removing sialic acid into glycolipid GA2 which further processed by β-Hexosaminidase B, thereby bypassing the HexA defect.