Huntington's disease (HD) is an inherited, progressive neurological disorder 
caused by a CAG/polyglutamine repeat expansion, for which there is no effective 
disease modifying therapy. In recent years, transcriptional dysregulation has 
emerged as a pathogenic process that appears early in disease progression. 
Administration of histone deacetylase (HDAC) inhibitors such as suberoylanilide 
hydroxamic acid (SAHA) have consistently shown therapeutic potential in models 
of HD, at least partly through increasing the association of acetylated histones 
with down-regulated genes and by correcting mRNA abnormalities. The HDAC enzyme 
through which SAHA mediates its beneficial effects in the R6/2 mouse model of HD 
is not known. Therefore, we have embarked on a series of genetic studies to 
uncover the HDAC target that is relevant to therapeutic development for HD. 
HDAC7 is of interest in this context because SAHA has been shown to decrease 
HDAC7 expression in cell culture systems in addition to inhibiting enzyme 
activity. After confirming that expression levels of Hdac7 are decreased in the 
brains of wild type and R6/2 mice after SAHA administration, we performed a 
genetic cross to determine whether genetic reduction of Hdac7 would alleviate 
phenotypes in the R6/2 mice. We found no improvement in a number of 
physiological or behavioral phenotypes. Similarly, the dysregulated expression 
levels of a number of genes of interest were not improved suggesting that 
reduction in Hdac7 does not alleviate the R6/2 HD-related transcriptional 
dysregulation. Therefore, we conclude that the beneficial effects of HDAC 
inhibitors are not predominantly mediated through the inhibition of HDAC7.