Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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.
Complete list of metadata

https://hal-univ-evry.archives-ouvertes.fr/hal-03433538
Contributor : Isabelle Richard Connect in order to contact the contributor
Submitted on : Wednesday, November 17, 2021 - 6:29:36 PM
Last modification on : Tuesday, November 30, 2021 - 3:26:38 AM

File

2021_Thiruvengadam et al_.pdf
Files produced by the author(s)

Identifiers

Citation

Girija Thiruvengadam, Sen Chandra Sreetama, Karine Charton, Marshall Hogarth, James Novak, et al.. Anoctamin 5 Knockout Mouse Model Recapitulates LGMD2L Muscle Pathology and Offers Insight Into in vivo Functional Deficits. Journal of Neuromuscular Diseases, IOS Press, 2021, pp.1-13. ⟨10.3233/JND-210720⟩. ⟨hal-03433538v1⟩

Share

Metrics

Record views

24

Files downloads

33