Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy.
Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy.
复制标题
A型层固定表达的丧失会损害导致肌营养不良症的核隐膜完整性。
DOI：
10.1083/jcb.147.5.913
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发表时间：
1999-11-29
影响因子：
7.8
通讯作者：
Burke, B
中科院分区：
文献类型：
--
作者：
Sullivan, T;Escalante-Alcalde, D;Bhatt, H;Anver, M;Bhat, N;Nagashima, K;Stewart, C L;Burke, B
核纤层是一种蛋白质网络内衬核内膜的核质面，并代表了一个重要的决定因素间期核架构。其主要成分是A型和B型核纤层蛋白。尽管B型核纤层蛋白存在于所有哺乳动物细胞中，但A型核纤层蛋白的表达受发育调节。在小鼠中，A型核纤层蛋白直到胚胎发育中期才出现，这表明这些蛋白可能参与终末分化的调节。在这里，我们发现缺乏A型核纤层蛋白的小鼠发育到足月时没有明显的异常。然而，他们出生后的生长严重迟缓，其特点是肌肉萎缩症的外观。这种表型与核膜的超微结构扰动有关。这些包括Emerin的错误定位，Emerin是一种内核膜蛋白，其缺陷与Emery-Dreifuss肌营养不良症（EDMD）（三种主要的X连锁营养不良症之一）有关。缺乏A型核纤层蛋白的小鼠表现出其核膜完整性和emerin分布的组织特异性改变。在骨骼肌和心肌中，这表现为与EDMD相关的营养不良状况。
The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin expression is developmentally regulated. In the mouse, A-type lamins do not appear until midway through embryonic development, suggesting that these proteins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnormalities. However, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy. This phenotype is associated with ultrastructural perturbations to the nuclear envelope. These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies. Mice lacking the A-type lamins exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as a dystrophic condition related to EDMD.