BioProject

Mutations in fukutin-related protein (FKRP) gene are characterized with a lack of functionally glycosylated α-dystroglycan (F-α-DG). More...

Mutations in fukutin-related protein (FKRP) gene are characterized with a lack of functionally glycosylated α-dystroglycan (F-α-DG). Surprisingly a small number of muscle fibers express strong F-α-DG. Here we investigate restoration of F-α-DG in FKRP mutant muscle and showed that the restoration of glycosylation is associated with muscle regeneration and dependent of the expression of both LARGE and partially functional FKRP. F-α-DG in regenerating fibers reaches normal levels and lasts for more than 4 weeks, however, no up-regulation of the LARGE and FKRP is detected during the regeneration process. These results suggest that FKRP P448L mutation clinically associated with severe CMD retains at least partial functions. Identification of factor(s) other than LARGE and FKRP could create new approaches for restoration of F-α-DG in mature muscle fibers with defects in FKRP function. We employed microarrays to detail changes in gene expression associated with muscle regeneration in wild-type and FKRP mutant skeletal muscle, and have identified a group of genes with altered expression between these mice during this regeneration process. Overall design: RNA from TA muscles of untreated control and i.m. NTX treated FKRP (P448L) mutant mice were compared by microarray at 2, 4, and 14 days post treatment to assess regenerative effects on gene expression. Less...