Decreased expression of striatal signaling genes in a mouse model of Huntington's disease

To understand gene expression changes mediated by a polyglutamine repeat ex pansion 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 encodi ng components of the neurotransmitter, calcium and retinoid signaling pathw ays 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 ind irectly reduces the expression of a distinct set of genes involved in signa ling pathways known to be critical to striatal neuron function.