Early postnatal death and motor disorders in mice congenitally deficient in calnexin expression
Early postnatal death and motor disorders in mice congenitally deficient in calnexin expression
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DOI：
10.1128/mcb.22.21.7398-7404.2002
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发表时间：
2002-11-01
影响因子：
5.3
通讯作者：
Owen, MJ
中科院分区：
文献类型：
--
作者：
Denzel, A;Molinari, M;Owen, MJ
钙连接蛋白是一种广泛表达的I型膜蛋白，其仅定位于内质网（ER）中。在哺乳动物细胞中，钙连接蛋白作为伴侣分子发挥作用，并通过其单葡萄糖基化聚糖与折叠中间体相互作用，在ER内的糖蛋白折叠和质量控制中发挥关键作用。为了更深入地了解钙连接蛋白的生理作用，我们已经产生了钙连接蛋白基因缺陷小鼠。尽管其深刻参与蛋白质折叠，钙连接蛋白是不是必不可少的胰岛细胞在体内的生存能力：钙连接蛋白基因敲除小鼠进行到足月，虽然50%的死亡在48小时内，大多数剩余的小鼠必须在4周内被处死，只有极少数小鼠存活至3个月。钙连接蛋白基因缺陷的小鼠比同窝出生的小鼠小，表现出非常明显的运动障碍，与大的有髓神经纤维的急剧损失有关。因此，钙连接蛋白对哺乳动物生理学的关键贡献是组织特异性的。
Calnexin is a ubiquitously expressed type I membrane protein which is exclusively localized in the endoplasmic reticulum (ER). In mammalian cells, calnexin functions as a chaperone molecule and plays a key role in glycoprotein folding and quality control within the ER by interacting with folding intermediates via their monoglucosylated glycans. In order to gain more insight into the physiological roles of calnexin, we have generated calnexin gene-deficient mice. Despite its profound involvement in protein folding, calnexin is not essential for mammalian-cell viability in vivo: calnexin gene knockout mice were carried to full term, although 50% died within 48 h and the majority of the remaining mice had to be sacrificed within 4 weeks, with only a very few mice surviving to 3 months. Calnexin gene-deficient mice were smaller than their littermates and showed very obvious motor disorders, associated with a dramatic loss of large myelinated nerve fibers. Thus, the critical contribution of calnexin to mammalian physiology is tissue specific.