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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

Zubeyde Bayram-Weston Orcid Logo, Timothy C. Stone, Peter Giles, Linda Elliston, Nari Janghra, Gemma V. Higgs, Peter A. Holmans, Stephen B. Dunnett, Simon P. Brooks, Lesley Jones Orcid Logo

BMC Genomics, Volume: 16, Issue: 1

Swansea University Author: Zubeyde Bayram-Weston Orcid Logo

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DOI (Published version): 10.1186/s12864-015-2251-4

Abstract

BackgroundThe 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...

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Published in: BMC Genomics
ISSN: 1471-2164
Published: Springer Science and Business Media LLC 2015
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URI: https://cronfa.swan.ac.uk/Record/cronfa46021
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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.ResultsDifferential 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.ConclusionsThe 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. 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spelling 2022-10-27T16:12:01.6417512 v2 46021 2018-11-21 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 93ba509b96e1eacf70cd2afd51361094 0000-0003-4560-8186 Zubeyde Bayram-Weston Zubeyde Bayram-Weston true false 2018-11-21 HEAL BackgroundThe 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.ResultsDifferential 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.ConclusionsThe 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. Journal Article BMC Genomics 16 1 Springer Science and Business Media LLC 1471-2164 Huntington’s disease; Neurodegeneration; Gene expression; Transgenic mouse models; Behaviour 21 12 2015 2015-12-21 10.1186/s12864-015-2251-4 COLLEGE NANME Healthcare Science COLLEGE CODE HEAL Swansea University This work was funded by CHDI and supported by an MRC studentship to ZB-W. We thank Central Biotechnology Services at the School of Medicine, Cardiff University, for technical support. 2022-10-27T16:12:01.6417512 2018-11-21T13:38:26.0500747 Faculty of Medicine, Health and Life Sciences School of Health and Social Care - Healthcare Science Zubeyde Bayram-Weston 0000-0003-4560-8186 1 Timothy C. Stone 2 Peter Giles 3 Linda Elliston 4 Nari Janghra 5 Gemma V. Higgs 6 Peter A. Holmans 7 Stephen B. Dunnett 8 Simon P. Brooks 9 Lesley Jones 0000-0002-3007-4612 10 46021__25601__745ac0ab0b534451b21fc529f7c1d7a9.pdf 46021.pdf 2022-10-27T16:10:51.7895007 Output 3010994 application/pdf Version of Record true © 2015 Bayram-Weston et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License true eng http://creativecommons.org/licenses/by/4.0/
title 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
spellingShingle 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
Zubeyde Bayram-Weston
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
author_id_str_mv 93ba509b96e1eacf70cd2afd51361094
author_id_fullname_str_mv 93ba509b96e1eacf70cd2afd51361094_***_Zubeyde Bayram-Weston
author Zubeyde Bayram-Weston
author2 Zubeyde Bayram-Weston
Timothy C. Stone
Peter Giles
Linda Elliston
Nari Janghra
Gemma V. Higgs
Peter A. Holmans
Stephen B. Dunnett
Simon P. Brooks
Lesley Jones
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container_title BMC Genomics
container_volume 16
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publishDate 2015
institution Swansea University
issn 1471-2164
doi_str_mv 10.1186/s12864-015-2251-4
publisher Springer Science and Business Media LLC
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str School of Health and Social Care - Healthcare Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}School of Health and Social Care - Healthcare Science
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description BackgroundThe 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.ResultsDifferential 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.ConclusionsThe 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.
published_date 2015-12-21T03:57:42Z
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