Figure 1.

Rpd3 is unique among the classic deacetylases in impacting degeneration: (A) heterozygous reduction of Rpd3 improves survival and (B) reduces neurodegeneration of flies challenged with Httex1p Q93; (C) the effect of heterozygous loss of each of the HDACs in Drosophila on survival to eclosion of Httex1p Q93-challenged animals was determined using multiple heterozygous mutations and/or shRNA constructs (one allele from each is shown here, for the full set of allele data see Supplementary Material, Fig. S1A and B). Only reduction of Rpd3 led to an increase in survival. Relative survival was calculated as (HDACHtt/HDACwt)/(ctrlHtt/ctrlwt), where ‘HDACHtt’ and ‘ctrlHtt’ is the number of eclosed elav > Httex1p Q93 flies with or without the HDAC mutation, and ‘HDACwt’ and ‘ctrlwt’ the eclosion number of the Htt non-expressing siblings with or without the HDAC mutation; (D) the effect of reduced HDAC levels on survival of neurons in Httex1p Q93-challenged animals. The results are shown as the difference in photoreceptor number compared with internal controls with a normal genetic background. Only Rpd3 leads to improved neuronal survival. The null allele of Rpd3 shown here, Rpd3[m5-5], reduces the extent of neuronal loss even more than a weaker hypomorphic allele (see panel B and Supplementary Material, Fig. S1B).