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Anoctamin 5 Knockout Mouse Model Recapitulates LGMD2L Muscle Pathology and Offers Insight Into in vivo Functional Deficits

Mutations in the Anoctamin 5 (Ano5) gene that result in the lack of expression or function of ANO5 protein, cause Limb Girdle Muscular Dystrophy (LGMD) 2L/R12, and Miyoshi Muscular Dystrophy (MMD3). However, the dystrophic phenotype observed in patient muscles is not uniformly recapitulated by ANO5...

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Autores principales: Thiruvengadam, Girija, Sreetama, Sen Chandra, Charton, Karine, Hogarth, Marshall, Novak, James S., Suel-Petat, Laurence, Chandra, Goutam, Allard, Bruno, Richard, Isabelle, Jaiswal, Jyoti K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673513/
https://www.ncbi.nlm.nih.gov/pubmed/34633328
http://dx.doi.org/10.3233/JND-210720
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author Thiruvengadam, Girija
Sreetama, Sen Chandra
Charton, Karine
Hogarth, Marshall
Novak, James S.
Suel-Petat, Laurence
Chandra, Goutam
Allard, Bruno
Richard, Isabelle
Jaiswal, Jyoti K.
author_facet Thiruvengadam, Girija
Sreetama, Sen Chandra
Charton, Karine
Hogarth, Marshall
Novak, James S.
Suel-Petat, Laurence
Chandra, Goutam
Allard, Bruno
Richard, Isabelle
Jaiswal, Jyoti K.
author_sort Thiruvengadam, Girija
collection PubMed
description Mutations in the Anoctamin 5 (Ano5) gene that result in the lack of expression or function of ANO5 protein, cause Limb Girdle Muscular Dystrophy (LGMD) 2L/R12, and Miyoshi Muscular Dystrophy (MMD3). However, the dystrophic phenotype observed in patient muscles is not uniformly recapitulated by ANO5 knockout in animal models of LGMD2L. Here we describe the generation of a mouse model of LGMD2L generated by targeted out-of-frame deletion of the Ano5 gene. This model shows progressive muscle loss, increased muscle weakness, and persistent bouts of myofiber regeneration without chronic muscle inflammation, which recapitulates the mild to moderate skeletal muscle dystrophy reported in the LGMD2L patients. We show that these features of ANO5 deficient muscle are not associated with a change in the calcium-activated sarcolemmal chloride channel activity or compromised in vivo regenerative myogenesis. Use of this mouse model allows conducting in vivo investigations into the functional role of ANO5 in muscle health and for preclinical therapeutic development for LGMD2L.
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spelling pubmed-86735132021-12-29 Anoctamin 5 Knockout Mouse Model Recapitulates LGMD2L Muscle Pathology and Offers Insight Into in vivo Functional Deficits Thiruvengadam, Girija Sreetama, Sen Chandra Charton, Karine Hogarth, Marshall Novak, James S. Suel-Petat, Laurence Chandra, Goutam Allard, Bruno Richard, Isabelle Jaiswal, Jyoti K. J Neuromuscul Dis Research Report Mutations in the Anoctamin 5 (Ano5) gene that result in the lack of expression or function of ANO5 protein, cause Limb Girdle Muscular Dystrophy (LGMD) 2L/R12, and Miyoshi Muscular Dystrophy (MMD3). However, the dystrophic phenotype observed in patient muscles is not uniformly recapitulated by ANO5 knockout in animal models of LGMD2L. Here we describe the generation of a mouse model of LGMD2L generated by targeted out-of-frame deletion of the Ano5 gene. This model shows progressive muscle loss, increased muscle weakness, and persistent bouts of myofiber regeneration without chronic muscle inflammation, which recapitulates the mild to moderate skeletal muscle dystrophy reported in the LGMD2L patients. We show that these features of ANO5 deficient muscle are not associated with a change in the calcium-activated sarcolemmal chloride channel activity or compromised in vivo regenerative myogenesis. Use of this mouse model allows conducting in vivo investigations into the functional role of ANO5 in muscle health and for preclinical therapeutic development for LGMD2L. IOS Press 2021-11-30 /pmc/articles/PMC8673513/ /pubmed/34633328 http://dx.doi.org/10.3233/JND-210720 Text en © 2021 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Report
Thiruvengadam, Girija
Sreetama, Sen Chandra
Charton, Karine
Hogarth, Marshall
Novak, James S.
Suel-Petat, Laurence
Chandra, Goutam
Allard, Bruno
Richard, Isabelle
Jaiswal, Jyoti K.
Anoctamin 5 Knockout Mouse Model Recapitulates LGMD2L Muscle Pathology and Offers Insight Into in vivo Functional Deficits
title Anoctamin 5 Knockout Mouse Model Recapitulates LGMD2L Muscle Pathology and Offers Insight Into in vivo Functional Deficits
title_full Anoctamin 5 Knockout Mouse Model Recapitulates LGMD2L Muscle Pathology and Offers Insight Into in vivo Functional Deficits
title_fullStr Anoctamin 5 Knockout Mouse Model Recapitulates LGMD2L Muscle Pathology and Offers Insight Into in vivo Functional Deficits
title_full_unstemmed Anoctamin 5 Knockout Mouse Model Recapitulates LGMD2L Muscle Pathology and Offers Insight Into in vivo Functional Deficits
title_short Anoctamin 5 Knockout Mouse Model Recapitulates LGMD2L Muscle Pathology and Offers Insight Into in vivo Functional Deficits
title_sort anoctamin 5 knockout mouse model recapitulates lgmd2l muscle pathology and offers insight into in vivo functional deficits
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673513/
https://www.ncbi.nlm.nih.gov/pubmed/34633328
http://dx.doi.org/10.3233/JND-210720
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