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Metadata

Name
Expression data from early symptomatic Sca1154Q/2Q and Sca7266Q/5Q knock-in cerebellum
Repository
Gemma
Identifier
gemma.experiment:1051
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.
Last Updated (by provider): Apr 15 2008
Contributors: Harry T Orr Chad A Shaw James P Carson Huda Y Zoghbi Christina Thaller Tao Zu Paymaan Jafar-Nejad Kei Watase Jennifer R Gatchel
Includes GDS3202.
Update date: Apr 21 2008.
Dataset description GDS3202: Analysis of cerebellum in spinocerebellar ataxia type 1 (SCA1) and type 7 (SCA7) knock-in models. SCA1 and SCA7 patients manifest cerebellar ataxia with degeneration of Purkinje cells. Results provide insight into the shared molecular pathogenic response in SCA1 and SCA7.
Data or Study Types
gene expression
Keywords
functional genomics
Source Organization
University of British Columbia
Access Conditions
available
Access Hyperlink
www.chibi.ubc.ca/Gemma/expressionExperiment/showExpressionExperiment.html?id=1051

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