000162193 001__ 162193
000162193 005__ 20190522142434.0
000162193 0247_ $$2doi$$a10.1093/hmg/ddq548
000162193 022__ $$a1460-2083
000162193 02470 $$2ISI$$a000287758600001
000162193 037__ $$aARTICLE
000162193 245__ $$aIn vivo cell-autonomous transcriptional abnormalities revealed in mice expressing mutant huntingtin in striatal but not cortical neurons
000162193 260__ $$c2011$$bOxford University Press
000162193 269__ $$a2011
000162193 336__ $$aJournal Articles
000162193 500__ $$aNational Licences
000162193 520__ $$aHuntington's disease (HD), caused by a CAG repeat expansion in the huntingtin (HTT) gene, is characterized by abnormal protein aggregates and motor and cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal medium spiny neuron (MSN) is most susceptible to dysfunction and death. Abnormal gene expression represents a core pathogenic feature of HD, but the relative roles of cell-autonomous and non-cell-autonomous effects on transcription remain unclear. To determine the extent of cell-autonomous dysregulation in the striatum in vivo, we examined genome-wide RNA expression in symptomatic D9-N171-98Q (a.k.a. DE5) transgenic mice in which the forebrain expression of the first 171 amino acids of human Htt with a 98Q repeat expansion is limited to MSNs. Microarray data generated from these mice were compared to those generated on the identical array platform from a pan-neuronal HD mouse model, R6/2, carrying two different CAG repeat lengths, and a relatively high degree of overlap of changes in gene expression was revealed. We further focused on known canonical pathways associated with excitotoxicity, oxidative stress, mitochondrial dysfunction, dopamine signaling and trophic support. While genes related to excitotoxicity, dopamine signaling and trophic support, were altered in both DE5 and R6/2 mice, which may be either cell-autonomous or non-cell-autonomous, genes related to mitochondrial dysfunction, oxidative stress and the peroxisome proliferator-activated receptor are primarily affected in DE5 transgenic mice, indicating cell autonomous mechanisms Overall, HD-induced dysregulation of the striatal transcriptome can be largely attributed to intrinsic effects of mutant Htt,,in the absence of expression in cortical neurons.
000162193 6531_ $$aDisease Transgenic Mice
000162193 6531_ $$aGene-Expression
000162193 6531_ $$aNeurodegenerative Diseases
000162193 6531_ $$aNeurological Symptoms
000162193 6531_ $$aNeurotrophic Factor
000162193 6531_ $$aRat Striatum
000162193 6531_ $$aTarget Genes
000162193 6531_ $$aMouse Model
000162193 6531_ $$aBrain
000162193 6531_ $$aDysregulation
000162193 700__ $$aThomas, Elizabeth A.
000162193 700__ $$aCoppola, Giovanni
000162193 700__ $$aTang, Bin
000162193 700__ $$aKuhn, Alexandre
000162193 700__ $$aKim, Soongho
000162193 700__ $$aGeschwind, Daniel H.
000162193 700__ $$aBrown, Timothy B.
000162193 700__ $$0240509$$g158211$$aLuthi-Carter, Ruth
000162193 700__ $$aEhrlich, Michelle E.
000162193 773__ $$j20$$tHuman molecular genetics$$k6$$q1049-1060
000162193 8564_ $$uhttps://infoscience.epfl.ch/record/162193/files/ddq548.pdf$$zPUBLISHER'S VERSION$$s519753
000162193 909C0 $$0252338$$pLNGF$$xU10838
000162193 909CO $$particle$$ooai:infoscience.tind.io:162193
000162193 917Z8 $$x182396
000162193 917Z8 $$x148230
000162193 937__ $$aEPFL-ARTICLE-162193
000162193 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000162193 980__ $$aARTICLE