Gene expression analysis on a single cell level in Purkinje cells of Huntington's disease transgenic mice

► Cerebellar neurodegeneration of purkinje cells in Huntington's Disease is well known. ► Microarray screening on Purkinje cells of R6/2 mice revealed downregulation of RORα-mediated mRNAs. ► Quantitative real time PCR and immunofluorescent staining corroborated these findings. ► The results overlap with changes in a model for spinocerebellar ataxia type 1. ► This suggests common pathogenic mechanisms for both polyglutamine diseases. Ataxia is a clinical feature of most polyglutamine disorders. Cerebellar neurodegeneration of Purkinje cells (PCs) in Huntington's Disease (HD) brain was described in the 1980s. PC death in the R6/2 transgenic model for HD was published by Turmaine et al. [27]. So far, PCs have not been examined on a single cell level. In order to begin to understand PC dysfunction and degeneration in HD we performed a gene expression study on laser-dissected PC based on a DNA microarray screening and quantitative real time PCR (Q-PCR). We demonstrate downregulation of the retinoid acid receptor-related orphan receptor α (RORα) mRNA and RORα-mediated mRNAs, also seen by immunofluorescent staining. As RORα and RORα-dependent transcriptional dysregulation is not only found in the R6/2 model for HD but also in a model for spinocerebellar ataxia type 1 (SCA1) (Serra et al. [24]) the data suggest common pathogenic mechanisms for both polyglutamine diseases.