The regenerative process in the murine model dy2J, with deficiency in a2-laminin

• Grant number: 23/14401-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mariz Vainzof
• Grantee: Luiza Albuquerque Coelho
• 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

Abstract

Skeletal muscle is a highly specialized tissue composed of multinucleated muscle fibers, with peripherally located nuclei, which contract to generate force in a controlled and directed manner. Muscular dystrophies are a group of diseases characterized by the progressive and irreversible loss of muscle cells, culminating in weakness and loss of motor capacity. The process of muscle degeneration stimulates the regeneration pathway, which attempts to repair the injured muscle through the activation of satellite cells that, when not stimulated, remain quiescent, but when stimulated and activated, induce muscle regeneration. However, this process is not efficient, as the loss of muscle mass is progressive. Humans and mice deficient in the ±2 subunit of the basement membrane protein, laminin 2/merosin, suffer from merosin-deficient congenital muscular dystrophy (CMD1A). The dy2J model mouse expresses a truncated ±2 chain and has a milder form of this disease. The objective of this project is to analyze the regenerative process in this dystrophic model, evaluating the proportion of quiescent and activated satellite cells, as well as the proportion of regenerating fibers, in the elderly animal compared to the juvenile animal. The effect of intense degeneration on the formation of tubular aggregates in senile muscle fibers, as occurs in normal elderly mice, will also be evaluated. There are still no studies analyzing the evolution of dystrophy in dy2J, so the investigation of this process is essential to better understand the dynamics of regeneration and degeneration in dystrophic muscles and may be useful for the treatment of patients with merosin congenital muscular dystrophy.