Adeno-associated virus-mediated overexpression of LARGE rescues α-dystroglycan function in dystrophic mice with mutations in the fukutin-related protein.

ABSTRACT: Multiple genes (e.g., POMT1, POMT2, POMGnT1, ISPD, GTDC2, B3GALNT2, FKTN, FKRP, and LARGE) are known to be involved in the glycosylation pathway of α-dystroglycan (α-DG). Mutations of these genes result in muscular dystrophies with wide phenotypic variability. Abnormal glycosylation of α-DG with decreased extracellular ligand binding activity is a common biochemical feature of these genetic diseases. While it is known that LARGE overexpression can compensate for defects in a few aforementioned genes, it is unclear whether it can also rescue defects in FKRP function. We examined adeno-associated virus (AAV)-mediated LARGE or FKRP overexpression in two dystrophic mouse models with loss-of-function mutations: (1) Large(myd) (LARGE gene) and (2) FKRP(P448L) (FKRP gene). The results agree with

SUBMITTER: Vannoy CH 

PROVIDER: S-EPMC4124536 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature