We have investigated the p53-dependent stress response in medium spiny neurons (MSNs) that degenerate in Huntington’s disease. To induce p53 signaling cascade, we have genetically inactivated by the Cre/loxP system the essential RNA polymerase I (Pol I) transcription factor TIF-IA, leading to stabilization of p53 and induction of p53-dependent apoptosis. In the present study, we selectively ablated the TIF-IA gene in MSNs by crossing TIF-IAflox/flox mice, homozygous for the floxed TIF-IA allele with transgenic mice expressing the Cre recombinase under the control of the D1 dopamine receptor (D1R) promoter. Overall design: To explore the molecular mechanisms underlying survival and death we profiled global gene expression in 9 and 13 week old control and TIF-IAD1RCre mutant mice (3 mice/each timepoint For each of the four conditions, five GeneChips were used each )