Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of ataxin-null (Atxn-null) vs. wild type mice to investigate spinocerebellar ataxia type 1 (SCA1)

ABSTRACT: Ataxin 1 (Atxn1) is a protein of unknown function associated with cerebellar neurodegeneration in spinocerebellar ataxia type 1 (SCA1). SCA1 is caused by an expanded polyglutamine within Atxn1 by gain-of-function mechanisms. Lack of Atxn1 in mice triggers motor deficits in the absence of neurodegeneration or apparent neuropathological abnormalities.We extracted RNA from cerebellum of 5 Atxn1-null mice and 5 WT. Cerebellar gene expression profiles at 15 weeks of age were generated usSCA1 ing Affymetrix MOE430A arrays. Identifying the molecular pathways regulated by Atxn1 can provide insights into the early molecular mechanisms underlying neuronal dysfunction.

ORGANISM(S): Mus musculus

SUBMITTER: Tamas Revesz

PROVIDER: E-MEXP-886 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Down-regulation of the dopamine receptor D2 in mice lacking ataxin 1.

Goold Robert R Hubank Michael M Hunt Abigail A Holton Janice J Menon Rajesh P RP Revesz Tamas T Pandolfo Massimo M Matilla-Dueñas Antoni A

Human molecular genetics 20070628 17

Ataxin 1 (Atxn1) is a protein of unknown function associated with spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease of late onset with variable degrees of cerebellar ataxia, ophthalmoplegia and neuropathy. SCA1 is caused by the toxic effects triggered by an expanded polyglutamine (polyQ) within Atxn1 resulting in neurodegeneration in the cerebellum, brain stem and spinocerebellar tracts. To gain insights into Atxn1 function, we have analysed the cerebellar gene expression profile ...[more]

PMID: 17599952

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Project description:Comparative analysis of cerebellar gene expression changes occurring in Sca1154Q/2Q and Sca7266Q/5Q knock-in mice; Polyglutamine diseases are inherited neurodegenerative disorders caused by expansion of CAG repeats encoding a glutamine tract in the disease-causing proteins. There are nine disorders each having distinct features but also clinical and pathological similarities. In particular, spinocerebellar ataxia type 1 and type 7 (SCA1 and SCA7) patients manifest cerebellar ataxia with degeneration of Purkinje cells. To determine whether the disorders share molecular pathogenic events, we studied two mouse models of SCA1 and SCA7 that express the glutamine-expanded protein from the respective endogenous loci. We found common transcriptional changes, with down-regulation of Insulin-like growth factor binding protein 5 (Igfbp5) representing one of the most robust changes. Igfbp5 down-regulation occurred in granule neurons through a non-cell autonomous mechanism and was concomitant with activation of of the Insulin-like growth factor (IGF) pathway and the type I IGF receptor on Purkinje cells. These data define one common pathogenic response in SCA1 and SCA7 and reveal the importance of intercellular mechanisms in their pathogenesis. Given that SCA1 and SCA7 share a cerebellar degenerative phenotype, we proposed that some shared molecular changes might occur in both diseases, and that common molecular alterations could pinpoint pathways that could be targeted to modulate or monitor the pathogenesis of more than one disease. We focused on transcriptional changes because both ATXN1 and ATXN7 play roles in transcriptional regulation and transcriptional defects can be detected in early-symptomatic stages of both SCA1 and SCA7 mouse models. To test our hypothesis, we examined cerebellar gene expression patterns in SCA1 and SCA7 knock-in (KI) models--Sca1154Q/2Q and Sca7266Q/5Q mice. Experiment Overall Design: Total cerebellar RNA samples were collected from Sca1154Q/2Q knock-in and wild type mice at the early symptomatic disease stage (4 weeks, n=3 knock-in and 3 wild type; 9-12 weeks, n=3 knock-in and 3 wild type). In parallel experiments, total cerebellar RNA samples were collected from Sca7266Q/5Q knock-in and wild type mice also at the early symptomatic disease stage (5 weeks, n=5 knock-in and 5 wild type).

Dataset Information

Transcription profiling of ataxin-null (Atxn-null) vs. wild type mice to investigate spinocerebellar ataxia type 1 (SCA1)

Publications

Down-regulation of the dopamine receptor D2 in mice lacking ataxin 1.

Similar Datasets

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