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Polyglutamine-induced neurodegeneration in SCA3 is not mitigated by non-expanded ataxin-3: conclusions from double-transgenic mouse models.

Abstract：

:A crucial question in polyQ-induced neurodegeneration is the influence of wild type protein on the formation of aggregates and toxicity. Recently it was shown that non-expanded ataxin-3 protein mitigated neurodegeneration in a Drosophila and mouse model of SCA3. We now explored the effects of overexpressing non-expanded ataxin-3 with 15Q in a SCA3 transgenic mouse model with 70 polyglutamine repeats. These double-transgenic mice (dt) developed neurological symptoms with premature death at the age of 6 months comparable to the single-transgenic (st) SCA3 disease model. Furthermore, immunohistochemistry revealed similar localization and distribution of nuclear aggregates in dt- and st-mutant SCA3 mice. In a second dt-mutant mouse model, coexpression of ataxin-3 with 148Q attached to a nuclear export signal, which usually diminishes the phenotype, did even reinforce toxic effects of mutant expanded ataxin-3. We therefore conclude that overexpressing wild type ataxin-3 or mutant ataxin-3 with NES are not striking suppressors of polyglutamine-induced neurodegeneration and have thus no potential for future gene therapeutic interventions in SCA3.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Hübener J,Riess O

doi

10.1016/j.nbd.2010.01.005

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

116-24

issue

1

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(10)00007-0

journal_volume

38

pub_type

杂志文章

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