Dataset Information


Abnormal Skeletal Muscle Regeneration plus Mild Alterations in Mature Fiber Type Specification in Fktn-Deficient Dystroglycanopathy Muscular Dystrophy Mice.

ABSTRACT: Glycosylated ?-dystroglycan provides an essential link between extracellular matrix proteins, like laminin, and the cellular cytoskeleton via the dystrophin-glycoprotein complex. In secondary dystroglycanopathy muscular dystrophy, glycosylation abnormalities disrupt a complex O-mannose glycan necessary for muscle structural integrity and signaling. Fktn-deficient dystroglycanopathy mice develop moderate to severe muscular dystrophy with skeletal muscle developmental and/or regeneration defects. To gain insight into the role of glycosylated ?-dystroglycan in these processes, we performed muscle fiber typing in young (2, 4 and 8 week old) and regenerated muscle. In mice with Fktn disruption during skeletal muscle specification (Myf5/Fktn KO), newly regenerated fibers (embryonic myosin heavy chain positive) peaked at 4 weeks old, while total regenerated fibers (centrally nucleated) were highest at 8 weeks old in tibialis anterior (TA) and iliopsoas, indicating peak degeneration/regeneration activity around 4 weeks of age. In contrast, mature fiber type specification at 2, 4 and 8 weeks old was relatively unchanged. Fourteen days after necrotic toxin-induced injury, there was a divergence in muscle fiber types between Myf5/Fktn KO (skeletal-muscle specific) and whole animal knockout induced with tamoxifen post-development (Tam/Fktn KO) despite equivalent time after gene deletion. Notably, Tam/Fktn KO retained higher levels of embryonic myosin heavy chain expression after injury, suggesting a delay or abnormality in differentiation programs. In mature fiber type specification post-injury, there were significant interactions between genotype and toxin parameters for type 1, 2a, and 2x fibers, and a difference between Myf5/Fktn and Tam/Fktn study groups in type 2b fibers. These data suggest that functionally glycosylated ?-dystroglycan has a unique role in muscle regeneration and may influence fiber type specification post-injury.


PROVIDER: S-EPMC4708996 | BioStudies | 2016-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC3428090 | BioStudies
2009-01-01 | S-EPMC2698593 | BioStudies
2019-01-01 | S-EPMC6744452 | BioStudies
1000-01-01 | S-EPMC4873967 | BioStudies
2012-01-01 | S-EPMC3428106 | BioStudies
2016-01-01 | S-EPMC4913802 | BioStudies
2004-01-01 | S-EPMC406392 | BioStudies
2013-01-01 | S-EPMC3577798 | BioStudies
1000-01-01 | S-EPMC4618654 | BioStudies
2009-01-01 | S-EPMC2655214 | BioStudies