Juvenile and adult expression of polyglutamine expandedhuntingtinproduce distinct aggregate distributions inDrosophilamuscle

Abstract

While Huntington's disease (HD) is widely recognized as a disease affecting the nervous system, much evidence has accumulated to suggest peripheral or non-neuronal tissues are affected as well. Here, we utilize the UAS/GAL4 system to express a pathogenic HD construct in the muscle of the fly, and characterize the effects. We observe detrimental phenotypes such as reduced lifespan, decreased locomotion, and accumulation of protein aggregates. Strikingly, depending on the GAL4 driver used to express the construct we saw different aggregate distributions and severity of phenotypes. These different aggregate distributions were found to be dependent on expression level and the timing of expression. Hsp70, a well-documented suppressor of polyglutamine aggregates, was found to strongly reduce the accumulation of aggregates in the eye, but in the muscle it did not prevent the reduction of the lifespan. Therefore, the molecular mechanisms underlying the detrimental effects of aggregates in the muscle are distinct from the nervous system.