Expression of glycosylated α‐dystroglycan in newborn skeletal and cardiac muscles of fukutin related protein (FKRP) mutant mice

ABSTRACT Introduction: Mutations in the Fukutin related protein (FKRP) gene are characterized by a lack of functionally glycosylated α‐dystroglycan (F‐α‐DG) in muscles. A small number of fibers retain the capacity to produce strong IIH6 reactive glycosylated‐α‐DG (g‐α‐DG) in muscles of both FKRP mutant animals and patients. Methods: We examined the expression of g‐α‐DG in limb, diaphragm, and cardiac muscles of newborn FKRP mutants and LARGEmyd mice with IIH6 antibody. Results: Near‐normal levels of g‐α‐DG were detected in all 3 muscles in the FKRP448LNeo‐ mutant. Expression was limited within the first 8 postnatal days with decreasing levels. No expression was identified in LARGEmyd mice. Conclusions: Temporary expression of glycosylated‐α‐DG in newborn FKRP mutant muscles is LARGE‐ and mutant FKRP‐dependent. The capability of mutant FKRP with a severe clinic phenotype to produce glycosylated‐α‐DG provides a new perspective for possible approaches to mitigate FKRP deficiency. Muscle Nerve 55: 582–590, 2017