A genetic model for muscle-eye-brain disease in mice lacking protein O-mannose 1,2-N-acetylglucosaminyltransferase (POMGnT1)

Protein O-mannose beta 1,2-N-acetyglucosaminyltransferase l (POMGnTI) is an enzyme involved in the synthesis of O-mannosyl glycans. Mutations of POMGnTl in humans result in the muscle-eye-brain (MEB) disease. In this study, we have characterized a null mutation generated by gene trapping with a retroviral vector inserted into the second exon of the mouse POMGnTl locus. Expression of POMGnTI mRNA was abolished in mutant mice. Glycosylation of alpha-dystroglycan was also reduced. POMGnTI mutant mice were viable with multiple developmental defects in muscle, eye, and brain, similar to the phenotypes observed in human MEB disease. The present study provides the first genetic animal model to further dissect the roles of POMGnTI in MEB disease. (c) 2006 Elsevier Ireland Ltd. All rights reserved.