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Onset and Progression of Behavioral and Molecular Phenotypes in a Novel Congenic R6/2 Line Exhibiting Intergenerational CAG Repeat Stability

In the present study we report on the use of speed congenics to generate a C57BL/6J congenic line of HD-model R6/2 mice carrying 110 CAG repeats, which uniquely exhibits minimal intergenerational instability. We also report the first identification of the R6/2 transgene insertion site. The relativel...

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Autores principales: Cowin, Randi-Michelle, Bui, Nghiem, Graham, Deanna, Green, Jennie R., Grueninger, Stephan, Yuva-Paylor, Lisa A., Syed, Arsalan U., Weiss, Andreas, Paylor, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233565/
https://www.ncbi.nlm.nih.gov/pubmed/22163300
http://dx.doi.org/10.1371/journal.pone.0028409
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author Cowin, Randi-Michelle
Bui, Nghiem
Graham, Deanna
Green, Jennie R.
Grueninger, Stephan
Yuva-Paylor, Lisa A.
Syed, Arsalan U.
Weiss, Andreas
Paylor, Richard
author_facet Cowin, Randi-Michelle
Bui, Nghiem
Graham, Deanna
Green, Jennie R.
Grueninger, Stephan
Yuva-Paylor, Lisa A.
Syed, Arsalan U.
Weiss, Andreas
Paylor, Richard
author_sort Cowin, Randi-Michelle
collection PubMed
description In the present study we report on the use of speed congenics to generate a C57BL/6J congenic line of HD-model R6/2 mice carrying 110 CAG repeats, which uniquely exhibits minimal intergenerational instability. We also report the first identification of the R6/2 transgene insertion site. The relatively stable line of 110 CAG R6/2 mice was characterized for the onset of behavioral impairments in motor, cognitive and psychiatric-related phenotypes as well as the progression of disease-related impairments from 4 to 10 weeks of age. 110Q mice exhibited many of the phenotypes commonly associated with the R6/2 model including reduced activity and impairments in rotarod performance. The onset of many of the phenotypes occurred around 6 weeks and was progressive across age. In addition, some phenotypes were observed in mice as early as 4 weeks of age. The present study also reports the onset and progression of changes in several molecular phenotypes in the novel R6/2 mice and the association of these changes with behavioral symptom onset and progression. Data from TR-FRET suggest an association of mutant protein state changes (soluble versus aggregated) in disease onset and progression.
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spelling pubmed-32335652011-12-12 Onset and Progression of Behavioral and Molecular Phenotypes in a Novel Congenic R6/2 Line Exhibiting Intergenerational CAG Repeat Stability Cowin, Randi-Michelle Bui, Nghiem Graham, Deanna Green, Jennie R. Grueninger, Stephan Yuva-Paylor, Lisa A. Syed, Arsalan U. Weiss, Andreas Paylor, Richard PLoS One Research Article In the present study we report on the use of speed congenics to generate a C57BL/6J congenic line of HD-model R6/2 mice carrying 110 CAG repeats, which uniquely exhibits minimal intergenerational instability. We also report the first identification of the R6/2 transgene insertion site. The relatively stable line of 110 CAG R6/2 mice was characterized for the onset of behavioral impairments in motor, cognitive and psychiatric-related phenotypes as well as the progression of disease-related impairments from 4 to 10 weeks of age. 110Q mice exhibited many of the phenotypes commonly associated with the R6/2 model including reduced activity and impairments in rotarod performance. The onset of many of the phenotypes occurred around 6 weeks and was progressive across age. In addition, some phenotypes were observed in mice as early as 4 weeks of age. The present study also reports the onset and progression of changes in several molecular phenotypes in the novel R6/2 mice and the association of these changes with behavioral symptom onset and progression. Data from TR-FRET suggest an association of mutant protein state changes (soluble versus aggregated) in disease onset and progression. Public Library of Science 2011-12-07 /pmc/articles/PMC3233565/ /pubmed/22163300 http://dx.doi.org/10.1371/journal.pone.0028409 Text en Cowin et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Cowin, Randi-Michelle
Bui, Nghiem
Graham, Deanna
Green, Jennie R.
Grueninger, Stephan
Yuva-Paylor, Lisa A.
Syed, Arsalan U.
Weiss, Andreas
Paylor, Richard
Onset and Progression of Behavioral and Molecular Phenotypes in a Novel Congenic R6/2 Line Exhibiting Intergenerational CAG Repeat Stability
title Onset and Progression of Behavioral and Molecular Phenotypes in a Novel Congenic R6/2 Line Exhibiting Intergenerational CAG Repeat Stability
title_full Onset and Progression of Behavioral and Molecular Phenotypes in a Novel Congenic R6/2 Line Exhibiting Intergenerational CAG Repeat Stability
title_fullStr Onset and Progression of Behavioral and Molecular Phenotypes in a Novel Congenic R6/2 Line Exhibiting Intergenerational CAG Repeat Stability
title_full_unstemmed Onset and Progression of Behavioral and Molecular Phenotypes in a Novel Congenic R6/2 Line Exhibiting Intergenerational CAG Repeat Stability
title_short Onset and Progression of Behavioral and Molecular Phenotypes in a Novel Congenic R6/2 Line Exhibiting Intergenerational CAG Repeat Stability
title_sort onset and progression of behavioral and molecular phenotypes in a novel congenic r6/2 line exhibiting intergenerational cag repeat stability
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233565/
https://www.ncbi.nlm.nih.gov/pubmed/22163300
http://dx.doi.org/10.1371/journal.pone.0028409
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