Analysis of galectin-1 expression and cellular localization in mdx mice skeletal muscle during the first cycle of muscle degeneration

Abstract

Duchenne Muscular Dystrophy (DMD) is a neuromuscular disease caused by the absence of dystrophin, a cytoskeleton protein which connects actin to the extracellular matrix. There is a progressive muscular degeneration which eventually leads to early death by respiratory and/or cardiac failure. The mdx mouse, an animal model of DMD, presents sarcolemmal instability, increase of serum creatine kinase and cycles of muscular degeneration/ regeneration; the first one begins between the second and third week postnatal. Galectin 1 is a lectin with affinity by -galactosides and participates in several processes like cellular adhesion, proliferation, apoptosis, tumorigenesis, phagocytosis, inflammatory response, immune reactions, differentiation and muscular regeneration. In proliferating myoblasts, galectin 1 presents low expression and cytoplasmic localization. During fusion and differentiation in myotubes, the expression increases and the protein is secreted. Since galectin 1 is involved in muscular regeneration and differentiation, this project aims to analyse its expression and localization in muscles of mdx during the first degeneration/regeneration cycle. Three-week-old mice (mdx and normal) will be analysed weekly until the sixth week. The evaluation of galectin 1 levels will be done in gastrocnemius and diaphragm muscles by semiquantitative RT-PCR and western blot. The cellular localization will be analyzed by immunohistochemistry. It will be evaluated the degree of muscular degeneration (using Evans blue) and regeneration (number of fibers with central nucleus). This project will contribute to the better understanding of the galectin 1 role in muscular function. Furthermore, it can give insights to propose therapeutic approaches to DMD based on the supplementation or inhibition of this lectin.