Huntington's disease (HD), caused by a CAG repeat expansion in the huntingtin 
(HTT) gene, is characterized by abnormal protein aggregates and motor and 
cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal 
medium spiny neuron (MSN) is most susceptible to dysfunction and death. Abnormal 
gene expression represents a core pathogenic feature of HD, but the relative 
roles of cell-autonomous and non-cell-autonomous effects on transcription remain 
unclear. To determine the extent of cell-autonomous dysregulation in the 
striatum in vivo, we examined genome-wide RNA expression in symptomatic 
D9-N171-98Q (a.k.a. DE5) transgenic mice in which the forebrain expression of 
the first 171 amino acids of human Htt with a 98Q repeat expansion is limited to 
MSNs. Microarray data generated from these mice were compared with those 
generated on the identical array platform from a pan-neuronal HD mouse model, 
R6/2, carrying two different CAG repeat lengths, and a relatively high degree of 
overlap of changes in gene expression was revealed. We further focused on known 
canonical pathways associated with excitotoxicity, oxidative stress, 
mitochondrial dysfunction, dopamine signaling and trophic support. While genes 
related to excitotoxicity, dopamine signaling and trophic support were altered 
in both DE5 and R6/2 mice, which may be either cell autonomous or non-cell 
autonomous, genes related to mitochondrial dysfunction, oxidative stress and the 
peroxisome proliferator-activated receptor are primarily affected in DE5 
transgenic mice, indicating cell-autonomous mechanisms. Overall, HD-induced 
dysregulation of the striatal transcriptome can be largely attributed to 
intrinsic effects of mutant Htt, in the absence of expression in cortical 
neurons.