Table I.
Mouse models of human GSL storage disease
| Disease | Lifespan | Defect | Major storage GSLs |
|---|---|---|---|
| Tay-Sachs | 2 yr | β-hexosaminidase A | Minor storage of GM2 and GA2 |
| aLOTS | 2 yr | β-hexosaminidase A | GM2 and GA2 |
| Sandhoff | 4–5 mo | β-hexosaminidase A/B | GM2, GA2, and globoside |
| Fabry | 2 yr | α-galactosidase A | Gb3 |
| GM1 gangliosidosis | 7–9 mo | β-galactosidase | GM1 and GA1 |
| bNPC1 | 2.5 mo | NPC1 protein | GM2, GM3, GlcCer, and LacCer |
a
LOTS mice become symptomatic at 6–12 mo but live to 2 yr (reference 32). The Tay-Sachs mice typically remain healthy until 2 yr.
b
NPC1 is a transmembrane protein of the late endosome/lysosome, not a catabolic enzyme, in contrast with the enzyme deficiencies that characterize the other diseases.