Journal
HUMAN MOLECULAR GENETICS
Volume 9, Issue 9, Pages 1259-1271Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/9.9.1259
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Funding
- NINDS NIH HHS [NS16375, NS38144, NS10800] Funding Source: Medline
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To understand gene expression changes mediated by a polyglutamine repeat expansion in the human huntingtin protein, we used oligonucleotide DNA arrays to profile similar to 6000 striatal mRNAs in the R6/2 mouse, a transgenic Huntington's disease (HD) model. We found diminished levels of mRNAs encoding components of the neurotransmitter, calcium and retinoid signaling pathways at both early and late symptomatic time points (6 and 12 weeks of age). We observed similar changes in gene expression in another HD mouse model (N171-82Q). These results demonstrate that mutant huntingtin directly or indirectly reduces the expression of a distinct set of genes involved in signaling pathways known to be critical to striatal neuron function.
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