Liu Jianmin, Ball Sherry L, Yang Yuan, Mei Pinchao, Zhang Lei, Shi Haining, Kaminski Henry J, Lemmon Vance P, Hu Huaiyu
Department of Neuroscience and Physiology, SUNY Upstate Medical University, 650 E. Adams Street, Syracuse, NY 13210, USA.
Mech Dev. 2006 Mar;123(3):228-40. doi: 10.1016/j.mod.2005.12.003. Epub 2006 Feb 3.
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.
蛋白质O-甘露糖β1,2-N-乙酰葡糖胺基转移酶1（POMGnT1）是一种参与O-甘露糖聚糖合成的酶。人类中POMGnT1的突变会导致肌肉-眼-脑（MEB）疾病。在本研究中，我们鉴定了一个通过基因捕获产生的无效突变，该突变由插入小鼠POMGnT1基因座第二个外显子的逆转录病毒载体引起。突变小鼠中POMGnT1 mRNA的表达被消除。α- dystroglycan的糖基化也减少。POMGnT1突变小鼠存活，但在肌肉、眼睛和大脑中存在多种发育缺陷，类似于人类MEB疾病中观察到的表型。本研究提供了第一个遗传动物模型，以进一步剖析POMGnT1在MEB疾病中的作用。
