Table 1.

Mouse Models of Sphingolipidoses

Mouse Models for the Disease	Enzyme Mutated	Phenotype and Features
Gaucher’s	Glucosylceramide-β-glucosidase	Animals die perinatally with accumulation of glucosylceramide in the lysosomes of the reticuloendothelial system [191].
Tay-Sach’s	α- chain of Hexosaminidase	Late onset behavioral changes Accumulation of GM2 in cerebral cortex, hippocampus, amygdala, hypothalamus, mamillary bodies etc [192].
Sandhoff	β- chain of Hexosaminidase	Show progressive motor incoordination and by 5 months almost gravely ill. Accumulation of PAS positive laden cells throughout the CNS [193].
Fabry Disease	Lysosomal α-galactosidase A	Accumulation of Gb3 in liver and Kidneys. Life span not affected till 80 wks [194, 195].
Krabbe Disease	Galactosylceramide-β-galactosidase	Twitcher mouse, die around 42 days. Accumulation of galactosylceramide and psychosine in the oligodendrocytes and Schwann cells with abundant cell death and dysmyelination of nerves. Increase in latency of neurotransmission [196].
Farber’s Disease	Acid-ceramidase	Embryonic lethal around 2 cell stage [197, 198]
Metachromatic leukodystrophy	Arylsulfatase A	Mice turn deaf because of loss of spiral ganglion cells. Reduced galactosylceramide and cholesterol [199, 200].
Niemann-Pick A	Acid Sphingomyelinase	Mice die between 4 and 6 months of age. Accumulation of sphingomyelin in vesicular structures of macrophages and reticuloendothelial cells. Degeneration of Purkinje cell layer of cerebellum that leads to impaired motor coordination [201].
Niemann-Pick C	NPC protein	Mice die around 10 weeks of age. (Accumulates unesterified cholesterol in many tissues. Age related loss of Purkinje cells in the Cerebellum [202]}.
	Neutral ceramidase	Inability of intestinal cells to metabolize dietary ceramide [203].
Sphingolipid activator proteins	Prosaposin (deletes A, B, C and D)	Symptoms early or late onset. Mice die neonatally or around 6 weeks of age. Hypomyelinated nerve fibers and complex sphingolipid accumulation in brain, liver and kidney
	Saposin A	Milder form compared knockout of all saposins
	Saposin C and D	Die by about 56 days but no myelination defect. However, these mice loose all their Purkinje cells by week 6 and accumulate glucosylceramide and α-hydroxy ceramides in brain and kidney reference [204-206]
GalNAcT	β1,4-N-acetylgalactosaminyltransferase	Wallerian degeneration of the myelinated neurons. Accumulation of GM3/GD3 lack of GM2/GD2
	Glucosylceramide synthase	Die during gastrulation due to enhanced apoptosis in the ectoderm. Conditional KO show loss of axonal branching in Purkinje cells [207-209]