Gene expression analysis on a single cell level in Purkinje cells of Huntington's disease transgenic mice.
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. 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 (ROR) mRNA and ROR-mediated mRNAs, also seen by immunofluorescent staining. As ROR and ROR-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.) the data suggest common pathogenic mechanisms for both polyglutamine diseases.
Department of Neurology, University Hospital, Freiburg, Germany.
Philipp
P
Euler
Bernd
B
Friedrich
Ruhtraut
R
Ziegler
Alexandre
A
Kuhn
Katrin S
KS
Lindenberg
Cornelius
C
Weiller
Birgit
B
Zucker
D000818:Animals; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics* / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism
D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D012333:RNA, Messenger