An Inducible Mouse Model of Late Onset Tay–Sachs Disease
Copyright policy )An Inducible Mouse Model of Late Onset Tay–Sachs Disease
Mouse models of the G(M2) gangliosidoses, Tay-Sachs and Sandhoff disease, are null for the hexosaminidase alpha and beta subunits respectively. The Sandhoff (Hexb-/-) mouse has severe neurological disease and mimics the human infantile onset variant. However, the Tay-Sachs (Hexa-/-) mouse model lacks an overt phenotype as mice can partially bypass the blocked catabolic pathway and escape disease. We have investigated whether a subset of Tay-Sachs mice develop late onset disease. We have found that approximately 65% of the mice develop one or more clinical signs of the disease within their natural life span (n = 52, P < 0.0001). However, 100% of female mice with repeat breeding histories developed late onset disease at an earlier age (n = 21, P < 0.0001) and displayed all clinical features. Repeat breeding of a large cohort of female Tay-Sachs mice confirmed that pregnancy induces late onset Tay-Sachs disease. Onset of symptoms correlated with reduced up-regulation of hexosaminidase B, a component of the bypass pathway.
- University of Southampton United Kingdom
- University of Bonn Germany
- University College London United Kingdom
- University of Oxford United Kingdom
Male, 570, hexosaminidase, 610, Neurosciences. Biological psychiatry. Neuropsychiatry, G(M2) Ganglioside, Mice, Pregnancy, GM2 gangliosidosis, Animals, Age of Onset, Muscle, Skeletal, Tay-Sachs Disease, glycosphingolipid, neurodegeneration, Brain, Mice, Mutant Strains, Mice, Inbred C57BL, Disease Models, Animal, Phenotype, lysosomal storage disease, Female, RC321-571
Male, 570, hexosaminidase, 610, Neurosciences. Biological psychiatry. Neuropsychiatry, G(M2) Ganglioside, Mice, Pregnancy, GM2 gangliosidosis, Animals, Age of Onset, Muscle, Skeletal, Tay-Sachs Disease, glycosphingolipid, neurodegeneration, Brain, Mice, Mutant Strains, Mice, Inbred C57BL, Disease Models, Animal, Phenotype, lysosomal storage disease, Female, RC321-571
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