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

被引：15

作者：

Giles, Peter ^{[1
]}

Elliston, Lyn ^{[1
]}

Higgs, Gemma V. ^{[2
]}

Brooks, Simon P. ^{[2
]}

Dunnett, Stephen B. ^{[2
]}

Jones, Lesley ^{[1
]}

机构：

[1] Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff CF14 4XN, S Glam, Wales

[2] Cardiff Univ, Sch Biosci, Brain Res Grp, Cardiff CF10 4AX, S Glam, Wales

来源：

BRAIN RESEARCH BULLETIN | 2012年 / 88卷 / 2-3期

关键词：

Huntington's disease; Neurodegeneration; Gene expression; Transgenic mouse models; Behaviour; TRANSGENIC MOUSE; TRANSCRIPTIONAL DYSREGULATION; TRINUCLEOTIDE REPEAT; BRAIN; MICE; PHENOTYPE; DEFICITS; ABNORMALITIES; MECHANISMS; PLASTICITY;

D O I：

10.1016/j.brainresbull.2011.10.001

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：199 / 209

页数：11

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