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Brain gene expression correlates with changes in behavior in the R6/1 mouse model of Huntington's disease

Hodges, Angela Kaye, Hughes, Gareth, Brooks, Simon Philip, Elliston, Linda Anne, Holmans, Peter Alan, Dunnett, Stephen Bruce and Jones, Lesley 2008. Brain gene expression correlates with changes in behavior in the R6/1 mouse model of Huntington's disease. Genes, Brain and Behavior 7 (3) , pp. 288-299. 10.1111/j.1601-183X.2007.00350.x

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Abstract

Huntington’s disease (HD) is an inherited neurodegeneration that causes a severe progressive illness and early death. Several animal models of the disease have been generated carrying the causativemutation and these have shown that one of the earliest molecular signs of the disease process is a substantial transcriptional deficit.We examined the alterations in brain gene expression in the R6/1 mouse line over the course of the development of phenotypic signs from 18 to 27 weeks. Changes in R6/1 mice were similar to those previously reported in R6/2 mice, and gene ontology analysis shows that pathways related to intracellular and electrical signaling are altered among downregulated genes and lipid biosynthesis and RNA processes among upregulated genes. The R6/1 mice showed deficits in rotarod performance, locomotor activity and exploratory behavior over the time–course. We have correlated the alterations in gene expression with changes in behavior seen in the mice and find that few alterations in gene expression correlate with all behavioral changes but rather that different subsets of the changes are uniquely correlated with one behavior only. This indicates that multiple behavioral tasks assessing different behavioral domains are likely to be necessary in therapeutic trials in mouse models of HD.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Biosciences
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Behavior; gene expression; Huntington’s disease; neurodegeneration; R6/1
Publisher: Blackwell Publishing
ISSN: 1601-1848
Last Modified: 21 Jun 2019 01:55
URI: http://orca.cf.ac.uk/id/eprint/27647

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