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An inducible mouse model of late onset Tay-Sachs disease

An inducible mouse model of late onset Tay-Sachs disease
An inducible mouse model of late onset Tay-Sachs disease
Mouse models of the GM2 gangliosidoses, Tay–Sachs and Sandhoff disease, are null for the hexosaminidase ? and ? 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.
GM2 gangliosidosis, lysosomal storage disease, glycosphingolipid, hexosaminidase, neurodegeneration
0969-9961
201-210
Jeyakumar, Mylvaganam
2afcb1bb-c6ff-4f74-9f75-5e1a4fd271c0
Smith, David
585b99c5-7a6c-49b5-92f4-68da743888de
Eliott-Smith, Elena
b5edbb9a-f93a-4aa7-9260-96e9c05b4a1a
Cortina-Borja, Mario
028ebae2-003d-413b-95cc-47d76914b006
Reinkensmeier, Gabriele
511115ff-208d-45fd-802c-4e2514f1f9bb
Butters, Terry D.
891552e5-fab9-49f8-9e0a-7fccb5920e35
Lemm, Thorsten
106c1ba5-ffe3-42ab-981a-f1044af79cf4
Sandhoff, Konrad
bca7ec1b-8236-4be7-9abf-5b3bd0b6a5b2
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Dwek, Raymond A.
d8d9d5f8-f2c0-414e-b6b0-df77a33f0da4
Platt, Frances M.
3b0d9f95-fba8-4083-91e2-c567c3e77582
Jeyakumar, Mylvaganam
2afcb1bb-c6ff-4f74-9f75-5e1a4fd271c0
Smith, David
585b99c5-7a6c-49b5-92f4-68da743888de
Eliott-Smith, Elena
b5edbb9a-f93a-4aa7-9260-96e9c05b4a1a
Cortina-Borja, Mario
028ebae2-003d-413b-95cc-47d76914b006
Reinkensmeier, Gabriele
511115ff-208d-45fd-802c-4e2514f1f9bb
Butters, Terry D.
891552e5-fab9-49f8-9e0a-7fccb5920e35
Lemm, Thorsten
106c1ba5-ffe3-42ab-981a-f1044af79cf4
Sandhoff, Konrad
bca7ec1b-8236-4be7-9abf-5b3bd0b6a5b2
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Dwek, Raymond A.
d8d9d5f8-f2c0-414e-b6b0-df77a33f0da4
Platt, Frances M.
3b0d9f95-fba8-4083-91e2-c567c3e77582

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), pp. 201-210. (doi:10.1006/nbdi.2002.0511).

Record type: Article

Abstract

Mouse models of the GM2 gangliosidoses, Tay–Sachs and Sandhoff disease, are null for the hexosaminidase ? and ? 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.

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Published date: August 2002
Keywords: GM2 gangliosidosis, lysosomal storage disease, glycosphingolipid, hexosaminidase, neurodegeneration

Identifiers

Local EPrints ID: 56108
URI: http://eprints.soton.ac.uk/id/eprint/56108
ISSN: 0969-9961
PURE UUID: 7e2d40d4-bf73-4d43-8e87-ab382eb9a899

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Date deposited: 07 Aug 2008
Last modified: 17 Jul 2017 14:31

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Contributors

Author: Mylvaganam Jeyakumar
Author: David Smith
Author: Elena Eliott-Smith
Author: Mario Cortina-Borja
Author: Gabriele Reinkensmeier
Author: Terry D. Butters
Author: Thorsten Lemm
Author: Konrad Sandhoff
Author: V. Hugh Perry
Author: Raymond A. Dwek
Author: Frances M. Platt

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