G.P.8 Expression analysis of α-dystroglycan glycosyltransferases in distinct murine muscular dystrophies models

Abstract

Dystroglycanopathies are genetic muscular dystrophies caused by defects in the glycosylation of α-dystroglycan (DG), an important component of the dystrophin-associated glycoprotein complex (DAG). There are at least six proven or putative glycosyltransferases enzymes, related to muscle diseases, which play a role in O-mannosyl-linked glycosylation of α-DG. In order to address the roles of α-dystroglycan glycosylation in distinct pathways of muscle degeneration and during muscle development we investigated the relative expression of four of them: POMT1, POMGnT1, LARGE and FKRP, in the gastrocnemius muscle from four mouse models for muscular dystrophies: Dmdmdx, Lama2dy2J/J, Largemyd, SJL/J, as compared to normal C57Black6 lineage. The study was done through real time PCR quantification, in three different ages: new born, 3 and 6months of age. In normal mice, a decreased expression with the age was observed for all genes, mainly for Fkrp and Large. In dystrophic lineages, we observed a large variation in the expression of the four glycosylation genes, as compared to normal age-matched mice. In new born, these differences were more significant and an upregulation was observed in Dmdmdx and Largemyd strains, while a downregulation, was detected in Lama2dy2J/J and SJL/J strains. In adult animals, the pattern was more close to normal mice of the same age. Our results suggest that an increase in α-dystroglycan glycosylation occurs during muscle development, and possibly also during the process of muscle regeneration. However, this process is variable in the diverse dystrophic strains. Financial support: FAPESP-CEPID, CNPq-INCT, FINEP, ABDIM.