Rewiring enervated: thinking LARGEr than myodystrophy.
LARGE is a glycosyltransferase known to glycosylate alpha-dystroglycan, a component of the dystrophin-associated glycoprotein complex. Spontaneous deletions in the Large gene (Large(myd) and Large(vls)) result in muscular dystrophy accompanied by heart, brain, and eye defects. Another Large mouse mutant, enervated (Large(enr)), is the result of a transgene integration event that disrupts Large gene expression. In addition to myodystrophy, enr mice have been shown to display peripheral nerve abnormalities, including altered axonal sorting resulting from Schwann cell defects, poor regeneration after nerve injury, and abnormal neuromuscular junctions. These data have provided new insight into our understanding of the function of LARGE and have suggested the possibility of involvement of substrates in addition to alpha-dystroglycan in the generation of the LARGE phenotype. The Large mutants are excellent models for addressing the importance of glycosylation in neuromuscular disease.
Levedakou
Eleni N
EN
Department of Neurology, Jack Miller Center for Peripheral Neuropathy, The University of Chicago, Illinois 60637, USA.
Popko
Brian
B
D000818:Animals; D002454:Cell Differentiation; D017353:Gene Deletion; D016695:Glycosyltransferases / Q000235:genetics*; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000294:innervation; D009136:Muscular Dystrophies / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation; D009469:Neuromuscular Junction / Q000201:enzymology* / Q000473:pathology; D017933:Peripheral Nervous System / Q000201:enzymology* / Q000473:pathology; D012583:Schwann Cells / Q000166:cytology / Q000201:enzymology; D019076:Transgenes
D016695:Glycosyltransferases