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

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.