Disease Progression Despite Early Loss of Polyglutamine Protein Expression in SCA7 Mouse Model - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Neuroscience Année : 2004

Disease Progression Despite Early Loss of Polyglutamine Protein Expression in SCA7 Mouse Model

Gretta Abou-Sleymane
  • Fonction : Auteur
Gaël Yvert
  • Fonction : Auteur
Stéphane Rousseau
Chantal Weber
  • Fonction : Auteur
Yvon Trottier
  • Fonction : Auteur
Jean-Louis Mandel
  • Fonction : Auteur
Didier Devys

Résumé

Nine neurodegenerative diseases including Huntington's disease (HD) and spinocerebellar ataxia type 7 (SCA7) are caused by an expansion of a polyglutamine (polyQ) stretch in the respective proteins. Aggregation of expanded polyQ-containing proteins into the nucleus is a hallmark of these diseases. Recent evidence indicates that transcriptional dysregulation may contribute to the molecular pathogen-esis of these diseases. Using SCA7 and HD mouse models in which we recently described a retinal phenotype, we investigated whether altered gene expression underlies photoreceptor dysfunction. In both models, rhodopsin promoter activity was early and dramatically repressed, suggesting that downregulation of photoreceptor-specific genes plays a major role in polyQ-induced retinal dysfunction. Because the rhodopsin promoter drives mutant ataxin-7 expression in our SCA7 mice, we also assessed whether downregulation of mutant SCA7 transgene would reverse retinopathy progression and aggregate formation. Although residual expression of mutant ataxin-7 was found negligible from 9 weeks of age, SCA7 transgenic mice showed a progressive decline of photoreceptor activity leading to a complete loss of electroretinographic responses from 1 year of age. At this age, aggregates were cleared in only half of the photore-ceptors, indicating that their formation is not fully reversible in this model. We demonstrate here that abolishing full-length mutant ataxin-7 expression did not reverse retinopathy progression in SCA7 mice, raising the possibility that some polyQ-induced pathological events might be irreversible.
Fichier principal
Vignette du fichier
HelmlingerJNeuro04.pdf (466 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02371887 , version 1 (05-11-2020)

Identifiants

Citer

D. Helmlinger, Gretta Abou-Sleymane, Gaël Yvert, Stéphane Rousseau, Chantal Weber, et al.. Disease Progression Despite Early Loss of Polyglutamine Protein Expression in SCA7 Mouse Model. Journal of Neuroscience, 2004, 24 (8), pp.1881-1887. ⟨10.1523/jneurosci.4407-03.2004⟩. ⟨hal-02371887⟩
21 Consultations
31 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More