Skeletal muscle regeneration is altered in the R6/2 mouse model of Huntington’s disease
Hoque, Sanzana LU ; Sjögren, Marie LU ; Allamand, Valérie LU ; Gawlik, Kinga LU ; Franke, Naomi ; Durbeej, Madeleine LU ; Björkqvist, Maria LU
and Soylu Kucharz, Rana
LU
(2022)
p.1-23
- Abstract
- Huntington’s disease (HD) is caused by CAG repeat expansion in the huntingtin (HTT) gene. Skeletal muscle wasting alongside central pathology is a well-recognized phenomenon seen in patients with HD and HD mouse models. HD muscle atrophy progresses with disease and affects prognosis and quality of life. Satellite cells, progenitors of mature skeletal muscle fibers, are essential for proliferation, differentiation, and repair of muscle tissue in response to muscle injury or exercise.
In this study, we aim to investigate the effect of mutant HTT on the differentiation and regeneration capacity of HD muscle by employing in vitro mononuclear skeletal muscle cell isolation and in vivo acute muscle damage model in R6/2 mice.
We... (More) - Huntington’s disease (HD) is caused by CAG repeat expansion in the huntingtin (HTT) gene. Skeletal muscle wasting alongside central pathology is a well-recognized phenomenon seen in patients with HD and HD mouse models. HD muscle atrophy progresses with disease and affects prognosis and quality of life. Satellite cells, progenitors of mature skeletal muscle fibers, are essential for proliferation, differentiation, and repair of muscle tissue in response to muscle injury or exercise.
In this study, we aim to investigate the effect of mutant HTT on the differentiation and regeneration capacity of HD muscle by employing in vitro mononuclear skeletal muscle cell isolation and in vivo acute muscle damage model in R6/2 mice.
We found that, similar to R6/2 adult mice, neonatal R6/2 mice also exhibit a significant reduction in myofiber width and morphological changes in gastrocnemius and soleus muscles compared to WT mice. Cardiotoxin (CTX)-induced acute muscle damage in R6/2 and WT mice showed that the Pax7+ satellite cell pool was dampened in R6/2 mice at 4 weeks post-injection, and R6/2 mice exhibited an altered inflammatory profile in response to acute damage.
Our results suggest that, in addition to the mutant HTT degenerative effects in mature muscle fibers, expression of mutant HTT in satellite cells might alter developmental and regenerative processes to contribute to the progressive muscle mass loss in HD. Taken together, the results presented here encourage further studies evaluating the underlying mechanisms of satellite cell dysfunction in HD mouse models. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/6e5baf78-2e62-4c24-99d4-6c68fae1dd4f
- author
- Hoque, Sanzana
LU
; Sjögren, Marie
LU
; Allamand, Valérie
LU
; Gawlik, Kinga
LU
; Franke, Naomi
; Durbeej, Madeleine
LU
; Björkqvist, Maria
LU
and Soylu Kucharz, Rana
LU
- organization
- publishing date
- 2022
- type
- Working paper/Preprint
- publication status
- published
- subject
- pages
- 1 - 23
- publisher
- bioRxiv
- DOI
- 10.1101/2022.01.11.475914
- language
- English
- LU publication?
- yes
- id
- 6e5baf78-2e62-4c24-99d4-6c68fae1dd4f
- date added to LUP
- 2022-01-30 12:46:55
- date last changed
- 2022-02-18 07:51:00
@misc{6e5baf78-2e62-4c24-99d4-6c68fae1dd4f,
abstract = {{Huntington’s disease (HD) is caused by CAG repeat expansion in the huntingtin (HTT) gene. Skeletal muscle wasting alongside central pathology is a well-recognized phenomenon seen in patients with HD and HD mouse models. HD muscle atrophy progresses with disease and affects prognosis and quality of life. Satellite cells, progenitors of mature skeletal muscle fibers, are essential for proliferation, differentiation, and repair of muscle tissue in response to muscle injury or exercise.<br/><br/>In this study, we aim to investigate the effect of mutant HTT on the differentiation and regeneration capacity of HD muscle by employing in vitro mononuclear skeletal muscle cell isolation and in vivo acute muscle damage model in R6/2 mice.<br/><br/>We found that, similar to R6/2 adult mice, neonatal R6/2 mice also exhibit a significant reduction in myofiber width and morphological changes in gastrocnemius and soleus muscles compared to WT mice. Cardiotoxin (CTX)-induced acute muscle damage in R6/2 and WT mice showed that the Pax7+ satellite cell pool was dampened in R6/2 mice at 4 weeks post-injection, and R6/2 mice exhibited an altered inflammatory profile in response to acute damage.<br/><br/>Our results suggest that, in addition to the mutant HTT degenerative effects in mature muscle fibers, expression of mutant HTT in satellite cells might alter developmental and regenerative processes to contribute to the progressive muscle mass loss in HD. Taken together, the results presented here encourage further studies evaluating the underlying mechanisms of satellite cell dysfunction in HD mouse models.}},
author = {{Hoque, Sanzana and Sjögren, Marie and Allamand, Valérie and Gawlik, Kinga and Franke, Naomi and Durbeej, Madeleine and Björkqvist, Maria and Soylu Kucharz, Rana}},
language = {{eng}},
note = {{Preprint}},
pages = {{1--23}},
publisher = {{bioRxiv}},
title = {{Skeletal muscle regeneration is altered in the R6/2 mouse model of Huntington’s disease}},
url = {{http://dx.doi.org/10.1101/2022.01.11.475914}},
doi = {{10.1101/2022.01.11.475914}},
year = {{2022}},
}