title: A genetic model for muscle-eye-brain disease in mice lacking protein O-mannose 1,2-N-acetylglucosaminyltransferase (POMGnT1).
abstract: Protein O-mannose beta1,2-N-acetyglucosaminyltransferase 1 (POMGnT1) is an enzyme involved in the synthesis of O-mannosyl glycans. Mutations of POMGnT1 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 POMGnT1 locus. Expression of POMGnT1 mRNA was abolished in mutant mice. Glycosylation of alpha-dystroglycan was also reduced. POMGnT1 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 POMGnT1 in MEB disease.
authors.affiliation: Department of Neuroscience and Physiology, SUNY Upstate Medical University, 650 E. Adams Street, Syracuse, NY 13210, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Liu
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Ball
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Pinchao
authors.initials: P
authors.lastname: Mei
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Haining
authors.initials: H
authors.lastname: Shi
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaminski
authors.forename: Vance P
authors.initials: VP
authors.lastname: Lemmon
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Hu
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D004195:Disease Models, Animal; D049030:Dystroglycans / Q000235:genetics; D005128:Eye Diseases / Q000473:pathology*; D005298:Fertility; D006031:Glycosylation; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D016548:Prosencephalon / Q000473:pathology
chemical_list: D049030:Dystroglycans; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase