Dystroglycanopathy muscles lacking functional glycosylation of alpha-dystroglycan retain regeneration capacity.

ABSTRACT

In dystroglycanopathies, lack of glycosylated alpha-dystroglycan (α-DG) alters membrane fragility leading to fiber damage and repetitive cycles of muscle degeneration and regeneration. However the effect of the glycosylation of α-DG on muscle regeneration is not clearly understood. In this study, we examined the regenerative capacity of dystrophic muscles in vivo in FKRP mutant and LARGE(myd) mice with little and complete lack of functionally glycosylated α-DG (F-α-DG) respectively. The number of regenerating fibers expressing embryonic myosin heavy chain (eMyHC) in the diseased muscles up to the age of 10 months is higher than or at similar levels to wild type muscle after notexin and polyethyleminine insults. The process of fiber maturation is not significantly affected by the lack of F-α-DG assessed by size distribution. The earlier appearance of a larger number of regenerating fibers after injury is consistent with the observation that the populations of myogenic satellite cells are increased and being readily activated in the dystroglycanopathy muscles. F-α-DG is expressed at trace amounts in undifferentiated myoblasts, but increases in differentiated myotubes in vitro. We therefore conclude that muscle regeneration is not impaired in the early stage of the dystroglycanopathies, and F-α-DG does not play a significant role in myogenic cell proliferation and fiber formation and maturation.