Distinct expression of functionally glycosylated alpha-dystroglycan in muscle and non-muscle tissues of FKRP mutant mice

PLoS One. 2018 Jan 10;13(1):e0191016. doi: 10.1371/journal.pone.0191016. eCollection 2018.

Abstract

The glycosylation of alpha-dystroglycan (α-DG) is crucial in maintaining muscle cell membrane integrity. Dystroglycanopathies are identified by the loss of this glycosylation leading to a breakdown of muscle cell membrane integrity and eventual degeneration. However, a small portion of fibers expressing functionally glycosylated α-DG (F-α-DG) (revertant fibers, RF) have been identified. These fibers are generally small in size, centrally nucleated and linked to regenerating fibers. Examination of different muscles have shown various levels of RFs but it is unclear the extent of which they are present. Here we do a body-wide examination of muscles from the FKRP-P448L mutant mouse for the prevalence of RFs. We have identified great variation in the distribution of RF in different muscles and tissues. Triceps shows a large increase in RFs and together with centrally nucleated fibers whereas the pectoralis shows a reduction in revertant but increase in centrally nucleated fibers from 6 weeks to 6 months of age. We have also identified that the sciatic nerve with near normal levels of F-α-DG in the P448Lneo- mouse with reduced levels in the P448Lneo+ and absent in LARGEmyd. The salivary gland of LARGEmyd mice expresses high levels of F-α-DG. Interestingly the same glands in the P448Lneo-and to a lesser degree in P448Lneo+ also maintain considerable amount of F-α-DG, indicating the non-proliferating epithelial cells have a molecular setting permitting glycosylation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dystroglycans / genetics
  • Dystroglycans / metabolism*
  • Glycosylation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Mutation*
  • N-Acetylglucosaminyltransferases / physiology*
  • Pentosyltransferases
  • Peripheral Nerves / metabolism*
  • Peripheral Nerves / pathology
  • Proteins / physiology*
  • Regeneration / physiology
  • Salivary Glands / metabolism*
  • Salivary Glands / pathology
  • Transferases

Substances

  • Dag1 protein, mouse
  • Proteins
  • Dystroglycans
  • Transferases
  • Large1 protein, mouse
  • N-Acetylglucosaminyltransferases
  • Fkrp protein, mouse
  • Pentosyltransferases

Grants and funding

This work was funded by the Carolinas Muscular Dystrophy Research Endowment at the Carolinas HealthCare Foundation (http://www.givecarolinas.org/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.