Journal
PROTEOMICS CLINICAL APPLICATIONS
Volume 2, Issue 12, Pages 1638-1650Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/prca.200800018
Keywords
Huntingtin; Protein expression; Time course; Transcriptome; Transgenic rat
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Polyglutamine-induced changes in gene expression have been demonstrated by using several mouse models of Huntington's disease (HD), which express extreme numbers of CAG repeats. We have recently developed a transgenic rat model of HD carrying a truncated huntingtin fragment with 51 CAG repeats, which is in the range seen in adult HD patients. For further evaluation, we have performed microarray analyses on whole brains of transgenic rats at 3 and 12 months of age and correlated it with protein expression by Western blot analysis. We found that genes functionally associated with gene expression and behavior were differently regulated already at 3 months of age, whereas at 12 months of age especially genes related to neurological diseases and cell-to-cell signaling and interaction were dysregulated. A detailed analysis of canonical pathways revealed that at 3 months of age genes in calcium signaling and synaptic long term potentation pathways were altered, while at 12 months of age, additionally, expression level of many genes implicated in Huntington's disease signaling, were changed.
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