Satellite cells deficiency and defective regeneration in dynamin 2-related centronuclear myopathy

Autor: Marc Bitoun, Camila F Almeida, Mariz Vainzof
Přispěvatelé: Universidade de São Paulo (USP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Myologie
Rok vydání: 2020
Předmět:
0301 basic medicine
Satellite Cells
Skeletal Muscle
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Biology
Biochemistry
Muscle hypertrophy
03 medical and health sciences
Dynamin II
Mice
0302 clinical medicine
satellite cell
dMyHC
Genetics
medicine
Animals
Regeneration
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Gene Knock-In Techniques
Centronuclear myopathy
Cytoskeleton
Muscle
Skeletal
Molecular Biology
Autosomal dominant centronuclear myopathy
Dynamin
electric induced
Regeneration (biology)
Muscle weakness
autosomal dominant centronuclear myopathy
developmental myosin heavy chain
medicine.disease
Cell biology
DNM2
030104 developmental biology
Gene Expression Regulation
Myogenic Regulatory Factors
Mutation
AD-CNM
cardiotoxin
medicine.symptom
030217 neurology & neurosurgery
Biotechnology
Myopathies
Structural
Congenital
Zdroj: FASEB Journal
FASEB Journal, Federation of American Society of Experimental Biology, 2021, 35 (4), pp.e21346. ⟨10.1096/fj.202001313rrr⟩
ISSN: 1530-6860
0892-6638
Popis: International audience; Dynamin 2 (DNM2) is a ubiquitously expressed protein involved in many functions related to trafficking and remodeling of membranes and cytoskeleton dynamics. Mutations in the DNM2 gene cause the autosomal dominant centronuclear myopathy (AD-CNM), characterized mainly by muscle weakness and central nuclei. Several defects have been identified in the KI-Dnm2R465W/+ mouse model of the disease to explain the muscle phenotype, including reduction of the satellite cell pool in muscle, but the functional consequences of this depletion have not been characterized until now. Satellite cells (SC) are the main source for muscle growth and regeneration of mature tissue. Here, we investigated muscle regeneration in the KI-Dnm2R465W/+ mouse model for AD-CNM. We found a reduced number of Pax7-positive SCs, which were also less activated after induced muscle injury. The muscles of the KI-Dnm2R465W/+ mouse regenerated more slowly and less efficiently than wild-type ones, formed fewer new myofibers, and did not recover its normal mass 15 days after injury. Altogether, our data provide evidence that the muscle regeneration is impaired in the KI-Dnm2R465W/+ mouse and contribute with one more layer to the comprehension of the disease, by identifying a new pathomechanism linked to DNM2 mutations which may be involved in the muscle-specific impact occurring in AD-CNM.
Databáze: OpenAIRE
Externí odkaz: