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Similar striatal gene expression profiles in the striatum of the YAC128 and HdhQ150 mouse models of Huntington's disease are not reflected in mutant Huntingtin inclusion prevalence

Bayram-Weston, Zubeyde, Stone, Timothy C., Giles, Peter James, Elliston, Linda Anne, Janghra, Narinder, Higgs, Gemma, Holmans, Peter Alan, Dunnett, Stephen Bruce, Brooks, Simon Philip and Jones, Lesley 2015. Similar striatal gene expression profiles in the striatum of the YAC128 and HdhQ150 mouse models of Huntington's disease are not reflected in mutant Huntingtin inclusion prevalence. BMC Genomics 16 , -. 10.1186/s12864-015-2251-4

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Abstract

Background The YAC128 model of Huntington’s disease (HD) shows substantial deficits in motor, learning and memory tasks and alterations in its transcriptional profile. We examined the changes in the transcriptional profile in the YAC128 mouse model of HD at 6, 12 and 18 months and compared these with those seen in other models and human HD caudate. Results Differential gene expression by genotype showed that genes related to neuronal function, projection outgrowth and cell adhesion were altered in expression. A Time-course ANOVA revealed that genes downregulated with increased age in wild-type striata were likely to be downregulated in the YAC128 striata. There was a substantial overlap of concordant gene expression changes in the YAC128 striata compared with those in human HD brain. Changes in gene expression over time showed fewer striatal YAC128 RNAs altered in abundance than in the HdhQ150 striata but there was a very marked overlap in transcriptional changes at all time points. Despite the similarities in striatal expression changes at 18 months the HdhQ150 mice showed widespread mHTT and ubiquitin positive inclusion staining in the striatum whereas this was absent in the YAC128 striatum. Conclusions The gene expression changes in YAC128 striata show a very closely matched profile to that of HdhQ150 striata and are already significantly different between genotypes by six months of age, implying that the temporal molecular gene expression profiles of these models match very closely, despite differences in the prevalence of brain inclusion formation between the models. The YAC128 gene expression changes appear to correlate well with gene expression differences caused by ageing. A relatively small number of genes showed significant differences in expression between the striata of the two models and these could explain some of the phenotypic differences between the models.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Biosciences
Neuroscience and Mental Health Research Institute (NMHRI)
Advanced Research Computing @ Cardiff (ARCCA)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: BioMed Central
ISSN: 1471-2164
Funders: CHDI
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 27 November 2015
Last Modified: 23 Aug 2019 11:15
URI: http://orca.cf.ac.uk/id/eprint/84461

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