Allelic series of Huntington's disease knock-in mice reveals expression discorrelates.

ABSTRACT: Identifying molecular drivers of pathology provides potential therapeutic targets. Differentiating between drivers and coincidental molecular alterations presents a major challenge. Variation unrelated to pathology further complicates transcriptomic, proteomic and metabolomic studies which measure large numbers of individual molecules. To overcome these challenges towards the goal of determining drivers of Huntington's disease (HD), we generated an allelic series of HD knock-in mice with graded levels of phenotypic severity for comparison with molecular alterations. RNA-sequencing analysis of this series reveals high numbers of transcripts with level alterations that do not correlate with phenotypic severity. These discorrelated molecular changes are unlikely to be drivers of pathology all

SUBMITTER: Kumar A 

PROVIDER: S-EPMC4805312 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature