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A novel Huntington's disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies

Huntington's disease (HD) is a fatal autosomal‐dominant neurodegenerative disease caused by a trinucleotide CAG repeat expansion of the huntingtin gene (HTT) that affects 1 in every 10 000 individuals in the United States. Our lab developed a novel immune deficient HD mouse strain, the YACNSG,...

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Autores principales: Dahlenburg, Heather, Cameron, David, Yang, Sheng, Bachman, Angelica, Pollock, Kari, Cary, Whitney, Pham, Missy, Hendrix, Kyle, White, Jeannine, Nelson, Haley, Deng, Peter, Anderson, Joseph S., Fink, Kyle, Nolta, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235129/
https://www.ncbi.nlm.nih.gov/pubmed/33710799
http://dx.doi.org/10.1002/sctm.20-0431
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author Dahlenburg, Heather
Cameron, David
Yang, Sheng
Bachman, Angelica
Pollock, Kari
Cary, Whitney
Pham, Missy
Hendrix, Kyle
White, Jeannine
Nelson, Haley
Deng, Peter
Anderson, Joseph S.
Fink, Kyle
Nolta, Jan
author_facet Dahlenburg, Heather
Cameron, David
Yang, Sheng
Bachman, Angelica
Pollock, Kari
Cary, Whitney
Pham, Missy
Hendrix, Kyle
White, Jeannine
Nelson, Haley
Deng, Peter
Anderson, Joseph S.
Fink, Kyle
Nolta, Jan
author_sort Dahlenburg, Heather
collection PubMed
description Huntington's disease (HD) is a fatal autosomal‐dominant neurodegenerative disease caused by a trinucleotide CAG repeat expansion of the huntingtin gene (HTT) that affects 1 in every 10 000 individuals in the United States. Our lab developed a novel immune deficient HD mouse strain, the YACNSG, from a commonly used line, the YAC128 mouse, to enable transplantation studies using engineered human cells in addition to studying the impact of the immune system on disease progression. The primary goal of this project was to characterize this novel immune deQficient HD mouse model, using behavioral assays and histology to compare this new model to the immune competent YAC128 and immune deficient mice that had engraftment of a human immune system. Flow cytometry was used to confirm that the YACNSG strain lacked immune cells, and in vivo imaging was used to assess human mesenchymal stem/stromal cell (MSC) retention compared with a commonly used immune deficient line, the NSG mouse. We found that YACNSG were able to retain human MSCs longer than the immune competent YAC128 mice. We performed behavioral assessments starting at 4 months of age and continued testing monthly until 12 months on the accelerod and in the open field. At 12 months, brains were isolated and evaluated using immunohistochemistry for striatal volume. Results from these studies suggest that the novel immune deficient YACNSG strain of mice could provide a good model for human stem‐cell based therapies and that the immune system appears to play an important role in the pathology of HD.
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spelling pubmed-82351292021-06-29 A novel Huntington's disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies Dahlenburg, Heather Cameron, David Yang, Sheng Bachman, Angelica Pollock, Kari Cary, Whitney Pham, Missy Hendrix, Kyle White, Jeannine Nelson, Haley Deng, Peter Anderson, Joseph S. Fink, Kyle Nolta, Jan Stem Cells Transl Med Enabling Technologies for Cell‐based Clinical Translation Huntington's disease (HD) is a fatal autosomal‐dominant neurodegenerative disease caused by a trinucleotide CAG repeat expansion of the huntingtin gene (HTT) that affects 1 in every 10 000 individuals in the United States. Our lab developed a novel immune deficient HD mouse strain, the YACNSG, from a commonly used line, the YAC128 mouse, to enable transplantation studies using engineered human cells in addition to studying the impact of the immune system on disease progression. The primary goal of this project was to characterize this novel immune deQficient HD mouse model, using behavioral assays and histology to compare this new model to the immune competent YAC128 and immune deficient mice that had engraftment of a human immune system. Flow cytometry was used to confirm that the YACNSG strain lacked immune cells, and in vivo imaging was used to assess human mesenchymal stem/stromal cell (MSC) retention compared with a commonly used immune deficient line, the NSG mouse. We found that YACNSG were able to retain human MSCs longer than the immune competent YAC128 mice. We performed behavioral assessments starting at 4 months of age and continued testing monthly until 12 months on the accelerod and in the open field. At 12 months, brains were isolated and evaluated using immunohistochemistry for striatal volume. Results from these studies suggest that the novel immune deficient YACNSG strain of mice could provide a good model for human stem‐cell based therapies and that the immune system appears to play an important role in the pathology of HD. John Wiley & Sons, Inc. 2021-03-12 /pmc/articles/PMC8235129/ /pubmed/33710799 http://dx.doi.org/10.1002/sctm.20-0431 Text en © 2021 The Authors. stem cells translational medicine published by Wiley Periodicals LLC on behalf of AlphaMed Press. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Enabling Technologies for Cell‐based Clinical Translation
Dahlenburg, Heather
Cameron, David
Yang, Sheng
Bachman, Angelica
Pollock, Kari
Cary, Whitney
Pham, Missy
Hendrix, Kyle
White, Jeannine
Nelson, Haley
Deng, Peter
Anderson, Joseph S.
Fink, Kyle
Nolta, Jan
A novel Huntington's disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies
title A novel Huntington's disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies
title_full A novel Huntington's disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies
title_fullStr A novel Huntington's disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies
title_full_unstemmed A novel Huntington's disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies
title_short A novel Huntington's disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies
title_sort novel huntington's disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies
topic Enabling Technologies for Cell‐based Clinical Translation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235129/
https://www.ncbi.nlm.nih.gov/pubmed/33710799
http://dx.doi.org/10.1002/sctm.20-0431
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