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Longitudinal analysis of gene expression and behaviour in the HdhQ150 mouse model of Huntington's disease

Giles, Peter James ORCID:, Elliston, Linda Anne, Higgs, Gemma, Brooks, Simon Philip ORCID:, Dunnett, Stephen Bruce ORCID: and Jones, Lesley ORCID: 2012. Longitudinal analysis of gene expression and behaviour in the HdhQ150 mouse model of Huntington's disease. Brain Research Bulletin 88 (2-3) , pp. 199-209. 10.1016/j.brainresbull.2011.10.001

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Substantial transcriptional changes are seen in Huntington's disease (HD) brain and parallel early changes in gene expression are observed in mouse models of HD. Analysis of behaviour in such models also shows substantial deficits in motor, learning and memory tasks. We examined the changes in the transcriptional profile in the HdhQ150 mouse model of HD at 6, 12 and 18 months and correlated these changes with the behavioural tasks the animals had undertaken. Changes in gene expression over time showed a significant enrichment of RNAs altered in abundance that related to cognition in both HdhQ150 and wild-type animals. The most significantly down-regulated mRNA between genotypes over the whole time-course was Htt itself. Other changes between genotypes identified at 6 months related to chromatin organization and structure, whilst at 18 months changes related mainly to intracellular signalling. Correlation of the changes in gene product abundance with phenotypic changes revealed that weight and detection of the opposite position of the platform in the water maze seemed to correlate with the chromatin alterations whereas changes in the rotarod performance related mainly to intracellular signalling and homeostasis. These results implicate alterations in specific molecular pathways that may underpin changes in different behavioural tasks.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
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: Huntington's disease; Neurodegeneration; Gene expression; Transgenic mouse models; Behaviour
Publisher: Elsevier
ISSN: 0361-9230
Last Modified: 11 Mar 2023 02:34

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