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Comparison of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development

Zubeyde Bayram-Weston Orcid Logo, Lesley Jones, Stephen B. Dunnett, Simon P. Brooks

PLOS ONE, Volume: 11, Issue: 5, Start page: e0155834

Swansea University Author: Zubeyde Bayram-Weston Orcid Logo

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DOI (Published version): 10.1371/journal.pone.0155834

Abstract

Huntington’s disease (HD) cellular pathology is characterised by the aggregation of mutant huntingtin (mHTT) protein into inclusion bodies. The present paper compared the sensitivity of five widely used mHTT antibodies (S830; MW8; EM48; 1C2; ubiquitin) against mice from five commonly used HD mouse m...

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ISSN: 1932-6203
Published: Public Library of Science (PLoS) 2016
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spelling 2022-10-27T16:00:39.6499316 v2 46020 2018-11-21 Comparison of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development 93ba509b96e1eacf70cd2afd51361094 0000-0003-4560-8186 Zubeyde Bayram-Weston Zubeyde Bayram-Weston true false 2018-11-21 HEAL Huntington’s disease (HD) cellular pathology is characterised by the aggregation of mutant huntingtin (mHTT) protein into inclusion bodies. The present paper compared the sensitivity of five widely used mHTT antibodies (S830; MW8; EM48; 1C2; ubiquitin) against mice from five commonly used HD mouse models (R6/1; YAC128; HdhQ92; B6 HdhQ150; B6 x129/Ola HdhQ150) at two ages to determine: the most sensitive antibodies for each model; whether mHTT antibody binding differed depending on aggregation stage (diffuse versus frank inclusion); the role of ubiquitin during aggregation as the ubiquitin proteosome system has been implicated in disease development. The models demonstrated unique profiles of antibody binding even when the models varied only by background strain (HdhQ150). MW8 was highly sensitive for detecting frank inclusions in all lines whereas EM48, ubiquitin and 1C2 demonstrated consistent staining in all models irrespective of age or form of mHTT. MW8 and S830 were the most sensitive antibodies with 1C2 the least. Ubiquitin levels were stable for each model regardless of age. Ubiquitin was particularly sensitive in young YAC128 mice that demonstrate an absence of inclusions until ~12 months of age suggesting high affinity to mHTT in its diffuse form. The data indicate that generalisations across models regarding the quantification of aggregations may not be valid and that mHTT antibody binding is unique to the mouse model and sensitive to changes in inclusion development. Journal Article PLOS ONE 11 5 e0155834 Public Library of Science (PLoS) 1932-6203 19 5 2016 2016-05-19 10.1371/journal.pone.0155834 COLLEGE NANME Healthcare Science COLLEGE CODE HEAL Swansea University This work was supported by the Cure Huntington's Disease Initiative (A5053;A6432 to SPB, LJ, SBD) (http://chdifoundation.org/) and the UK Medical Research Council Centenary Early Career Award (ZBW, SBD: MR/J500367/1) (www. mrc.ac.uk/). 2022-10-27T16:00:39.6499316 2018-11-21T13:37:38.8828477 Faculty of Medicine, Health and Life Sciences School of Health and Social Care - Healthcare Science Zubeyde Bayram-Weston 0000-0003-4560-8186 1 Lesley Jones 2 Stephen B. Dunnett 3 Simon P. Brooks 4 46020__25600__ea298e2666a84c519a11e0db508133d8.pdf 46020_VoR.pdf 2022-10-27T15:59:51.6551920 Output 2567541 application/pdf Version of Record true © 2016 Bayram-Weston et al. This is an open access article distributed under the terms of the Creative Commons Attribution License true eng http://creativecommons.org/licenses/by/4.0/
title Comparison of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development
spellingShingle Comparison of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development
Zubeyde Bayram-Weston
title_short Comparison of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development
title_full Comparison of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development
title_fullStr Comparison of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development
title_full_unstemmed Comparison of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development
title_sort Comparison of mHTT Antibodies in Huntington’s Disease Mouse Models Reveal Specific Binding Profiles and Steady-State Ubiquitin Levels with Disease Development
author_id_str_mv 93ba509b96e1eacf70cd2afd51361094
author_id_fullname_str_mv 93ba509b96e1eacf70cd2afd51361094_***_Zubeyde Bayram-Weston
author Zubeyde Bayram-Weston
author2 Zubeyde Bayram-Weston
Lesley Jones
Stephen B. Dunnett
Simon P. Brooks
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publishDate 2016
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publisher Public Library of Science (PLoS)
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title Faculty of Medicine, Health and Life Sciences
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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 Huntington’s disease (HD) cellular pathology is characterised by the aggregation of mutant huntingtin (mHTT) protein into inclusion bodies. The present paper compared the sensitivity of five widely used mHTT antibodies (S830; MW8; EM48; 1C2; ubiquitin) against mice from five commonly used HD mouse models (R6/1; YAC128; HdhQ92; B6 HdhQ150; B6 x129/Ola HdhQ150) at two ages to determine: the most sensitive antibodies for each model; whether mHTT antibody binding differed depending on aggregation stage (diffuse versus frank inclusion); the role of ubiquitin during aggregation as the ubiquitin proteosome system has been implicated in disease development. The models demonstrated unique profiles of antibody binding even when the models varied only by background strain (HdhQ150). MW8 was highly sensitive for detecting frank inclusions in all lines whereas EM48, ubiquitin and 1C2 demonstrated consistent staining in all models irrespective of age or form of mHTT. MW8 and S830 were the most sensitive antibodies with 1C2 the least. Ubiquitin levels were stable for each model regardless of age. Ubiquitin was particularly sensitive in young YAC128 mice that demonstrate an absence of inclusions until ~12 months of age suggesting high affinity to mHTT in its diffuse form. The data indicate that generalisations across models regarding the quantification of aggregations may not be valid and that mHTT antibody binding is unique to the mouse model and sensitive to changes in inclusion development.
published_date 2016-05-19T03:57:42Z
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