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Wild type huntingtin reduces the cellular toxicity of mutant huntingtin in mammalian cell models of Huntington's disease

Wild type huntingtin reduces the cellular toxicity of mutant huntingtin in mammalian cell models of Huntington's disease
Wild type huntingtin reduces the cellular toxicity of mutant huntingtin in mammalian cell models of Huntington's disease
OBJECTIVESRecent data suggest that wild type huntingtin can protect against apoptosis in the testis of mice expressing full length huntingtin transgenes with expanded CAG repeats. It is not clear if this protective effect was confined to particular cell types, or if wild type huntingtin exerted its protective effect in this model by simply reducing the formation of toxic proteolytic fragments from mutant huntingtin. METHODSWe cotransfected neuronal (SK-N-SH, human neuroblastoma) and non-neuronal (COS-7, monkey kidney) cell lines with HD exon 1 (containing either 21 or 72 CAG repeats) construct DNA and either full length wild type huntingtin or pFLAG (control vector). RESULTSFull length wild type huntingtin significantly reduced cell death resulting from the mutant HD exon 1 fragments containing 72 CAG repeats in both cell lines. Wild type huntingtin did not significantly modulate cell death caused by transfection of HD exon 1 fragments containing 21 CAG repeats in either cell line. CONCLUSIONSOur results suggest that wild type huntingtin can significantly reduce the cellular toxicity of mutant HD exon 1 fragments in both neuronal and non-neuronal cell lines. This suggests that wild type huntingtin can be protective in different cell types and that it can act against the toxicity caused by a mutant huntingtin fragment as well as against a full length transgene.
0022-2593
450-452
Ho, L.W.
15fd89cb-be65-4d19-bf27-66a168b52c8b
Brown, R.
b9108870-6092-4963-b323-be7254c71976
Maxwell, M.
938ddd59-cafd-4218-9dff-71b8a89eecb3
Wyttenbach, A.
69846a0f-fb60-4a28-84eb-ed865a5e31fa
Rubinsztein, D.C.
7bc49386-aa67-4658-a966-0d952e6fd731
Ho, L.W.
15fd89cb-be65-4d19-bf27-66a168b52c8b
Brown, R.
b9108870-6092-4963-b323-be7254c71976
Maxwell, M.
938ddd59-cafd-4218-9dff-71b8a89eecb3
Wyttenbach, A.
69846a0f-fb60-4a28-84eb-ed865a5e31fa
Rubinsztein, D.C.
7bc49386-aa67-4658-a966-0d952e6fd731

Ho, L.W., Brown, R., Maxwell, M., Wyttenbach, A. and Rubinsztein, D.C. (2001) Wild type huntingtin reduces the cellular toxicity of mutant huntingtin in mammalian cell models of Huntington's disease. Journal of Medical Genetics, 38, 450-452.

Record type: Article

Abstract

OBJECTIVESRecent data suggest that wild type huntingtin can protect against apoptosis in the testis of mice expressing full length huntingtin transgenes with expanded CAG repeats. It is not clear if this protective effect was confined to particular cell types, or if wild type huntingtin exerted its protective effect in this model by simply reducing the formation of toxic proteolytic fragments from mutant huntingtin. METHODSWe cotransfected neuronal (SK-N-SH, human neuroblastoma) and non-neuronal (COS-7, monkey kidney) cell lines with HD exon 1 (containing either 21 or 72 CAG repeats) construct DNA and either full length wild type huntingtin or pFLAG (control vector). RESULTSFull length wild type huntingtin significantly reduced cell death resulting from the mutant HD exon 1 fragments containing 72 CAG repeats in both cell lines. Wild type huntingtin did not significantly modulate cell death caused by transfection of HD exon 1 fragments containing 21 CAG repeats in either cell line. CONCLUSIONSOur results suggest that wild type huntingtin can significantly reduce the cellular toxicity of mutant HD exon 1 fragments in both neuronal and non-neuronal cell lines. This suggests that wild type huntingtin can be protective in different cell types and that it can act against the toxicity caused by a mutant huntingtin fragment as well as against a full length transgene.

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Published date: 1 July 2001

Identifiers

Local EPrints ID: 56766
URI: http://eprints.soton.ac.uk/id/eprint/56766
ISSN: 0022-2593
PURE UUID: 7d63ac8b-2e65-4c79-906a-37c31540523a

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Date deposited: 06 Aug 2008
Last modified: 08 Jan 2022 19:04

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Contributors

Author: L.W. Ho
Author: R. Brown
Author: M. Maxwell
Author: A. Wyttenbach
Author: D.C. Rubinsztein

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