An inducible mouse model of late onset Tay-Sachs disease


Jeyakumar, Mylvaganam, Smith, David, Eliott-Smith, Elena, Cortina-Borja, Mario, Reinkensmeier, Gabriele, Butters, Terry D., Lemm, Thorsten, Sandhoff, Konrad, Perry, V. Hugh, Dwek, Raymond A. and Platt, Frances M. (2002) An inducible mouse model of late onset Tay-Sachs disease. Neurobiology of Disease, 10, (3), 201-210. (doi:10.1006/nbdi.2002.0511).

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Original Publication URL: http://dx.doi.org/10.1006/nbdi.2002.0511

Description/Abstract

Mouse models of the GM2 gangliosidoses, Tay–Sachs and Sandhoff disease, are null for the hexosaminidase α and β 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 not, vert, similar65% 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.

Item Type: Article
ISSNs: 0969-9961 (print)
Related URLs:
Keywords: GM2 gangliosidosis, lysosomal storage disease, glycosphingolipid, hexosaminidase, neurodegeneration
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 56108
Date Deposited: 07 Aug 2008
Last Modified: 27 Mar 2014 18:38
URI: http://eprints.soton.ac.uk/id/eprint/56108

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