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Huntingtin inclusions do not down‐regulate specific genes in the R6/2 Huntington's disease mouse
Author(s) -
SadriVakili G.,
Me A. S.,
Farrell L. A.,
KellerMcGandy C. E.,
CantutiCastelvetri I.,
Standaert D. G.,
Augood S. J.,
Yohrling G. J.,
Cha J.H. J.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04871.x
Subject(s) - huntington's disease , huntingtin , biology , laser capture microdissection , huntingtin protein , gene , genetically modified mouse , transgene , striatum , in situ hybridization , messenger rna , transcriptional regulation , microbiology and biotechnology , gene expression , genetics , disease , neuroscience , pathology , mutant , medicine , dopamine
Transcriptional dysregulation is a central pathogenic mechanism in Huntington's disease (HD); HD and transgenic mouse models of HD demonstrate down‐regulation of specific genes at the level of mRNA expression. Furthermore, neuronal intranuclear inclusions (NIIs) have been identified in the brains of R6/2 mice and HD patients. One possibility is that NIIs contribute to transcriptional dysregulation by sequestering transcription factors. We therefore assessed the relationship between NIIs and transcriptional dysregulation in the R6/2 mouse, using double‐label in situ hybridization combined with immunohistochemistry, and laser capture microdissection combined with quantitative real‐time PCR. There was no difference in transcript levels of specific genes between NII‐positive and NII‐negative neurons. These results demonstrate that NIIs do not cause decreases in D2, PPE and PSS mRNA levels in R6/2 striatum and therefore are not involved in the down‐regulation of these specific genes in this HD model. In addition, these observations argue against the notion that NIIs protect against transcriptional dysregulation in HD.