PDF(Pubmed)
Abstract：
Dystroglycan (DG) is an extracellular matrix receptor consisting of an α- and a β-DG subunit encoded by the DAG1 gene. The homozygous mutation (c.2006G>T, p.Cys669Phe) in β-DG causes muscle-eye-brain disease with multicystic leukodystrophy in humans. In a mouse model of this primary dystroglycanopathy, approximately two-thirds of homozygous embryos fail to develop to term. Mutant mice that are born undergo a normal postnatal development but show a late-onset myopathy with partially penetrant histopathological changes and an impaired performance on an activity wheel. Their brains and eyes are structurally normal, but the localization of mutant β-DG is altered in the glial perivascular end-feet, resulting in a perturbed protein composition of the blood-brain and blood-retina barrier. In addition, α- and β-DG protein levels are significantly reduced in muscle and brain of mutant mice. Owing to the partially penetrant developmental phenotype of the C669F β-DG mice, they represent a novel and highly valuable mouse model with which to study the molecular effects of β-DG functional alterations both during embryogenesis and in mature muscle, brain and eye, and to gain insight into the pathogenesis of primary dystroglycanopathies.
摘要：
营养不良聚糖(DG)是由DAG1基因编码的α-和β-DG亚基组成的细胞外基质受体。纯合突变（c.2006G>T，β-DG中的p.Cys669Phe）引起人类多囊性脑白质营养不良的肌-眼-脑疾病。在这种原发性营养不良病的小鼠模型中，大约三分之二的纯合胚胎未能发育到足月。出生的突变小鼠经历正常的出生后发育，但表现出迟发性肌病，具有部分渗透性的组织病理学变化和活动轮上的表现受损。他们的大脑和眼睛结构正常，但是突变型β-DG的定位在神经胶质血管末足中被改变，导致血脑和血视网膜屏障的蛋白质组成受到干扰。此外,突变小鼠的肌肉和大脑中的α-和β-DG蛋白水平显着降低。由于C669F-β-DG小鼠的部分渗透发育表型，它们代表了一种新颖且非常有价值的小鼠模型，用于研究胚胎发生过程中和成熟肌肉中β-DG功能改变的分子效应，大脑和眼睛，并深入了解原发性营养不良病的发病机理。
