Study of the regenerative potential of satellite cells in centronuclear myopathy and myogenic capacity of its released microvesicles

• Grant number: 15/18914-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2016
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mariz Vainzof
• Grantee: Camila de Freitas Almeida
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID
• Associated scholarship(s): 17/07376-7 - Investigation of satellite cell behavior and extracellular vesicles in centronuclear myopathy, BE.EP.DR

Abstract

The adult muscle has an enormous regenerative capacity when damaged, growing new fibers or fixing the previous ones using progenitor cells with myogenic potential, named satellite cells. However, in neuromuscular disorders, both muscle development and regeneration are not efficient, causing muscle weakness and loss of motor ability.Among the many neuromuscular disorders, the centronuclear myopathies (CNM) comprise a subgroup characterized by the presence of muscle fibers with centralized nuclei. Three different forms are recognized, with mutations in the genes MTM1 (X-linked inheritance), BIN1 (autosomal recessive) and DNM2 (autosomal dominant). The knock-in murine model KI-Dnm2R465W bears the most frequent mutation found in CNM-AD patients and develops a mild myopathy, with modest muscle involvement and slight force reduction. This animal presents few centronucleated fibers and lack of an evident degeneration.A recent work showed alterations in satellite cells' quantity and behavior in a CNM mouse model with a mutation in MTM1. Thus, it is possible that regeneration in other CNM types could also be compromised. The regeneration process within the muscle affected by centronuclear myopathy with DNM2 mutations is not known, and its study is the main objective of this project. Satellite cell population and endocytosis process will be evaluated in CNM-AD-DNM2 patients and in its respective mouse model KI-Dnm2R465W. In the latter, muscle lesion will be induced by electroporation, to activate the degenerative-regenerative process. By using this approach, alterations are expected to be found in the regeneration which could help the search for new therapeutic targets.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

F. ALMEIDA, CAMILA; BITOUN, MARC; VAINZOF, MARIZ. Satellite cells deficiency and defective regeneration in dynamin 2-related centronuclear myopathy. FASEB JOURNAL, v. 35, n. 4, APR 2021. (17/07376-7, 13/08028-1, 15/18914-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ALMEIDA, Camila de Freitas. Skeletal muscle regeneration in DNM2-related centronuclear myopathy. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.