Gene targeting of envoplakin, a cytoskeletal linker protein and precursor of the epidermal cornified envelope
Gene targeting of envoplakin, a cytoskeletal linker protein and precursor of the epidermal cornified envelope
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DOI：
10.1128/mcb.21.20.7047-7053.2001
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发表时间：
2001-10-01
影响因子：
5.3
通讯作者：
Watt, FM
中科院分区：
文献类型：
--
作者：
Määttä, A;DiColandrea, T;Watt, FM
Envoplakin是细胞骨架连接蛋白plakin家族的一员，定位于复层上皮细胞的桥粒，是表皮角化包膜的组成部分。在小鼠胚胎干细胞中进行基因打靶，以产生零等位基因envoplakin。在新生小鼠的皮肤中没有检测到目标等位基因的envoplakin转录本。目标等位基因纯合的小鼠出生在正常的孟德尔比例中，并具有生育能力。直到一岁之前，他们没有发展出任何可辨别的病理表型。成体表皮角化包膜的超微结构外观在野生型和基因敲除小鼠之间难以区分，也没有证据表明Envoplakin的缺失影响了桥粒中发现的另外两种Plakin蛋白--周斑蛋白或桥粒蛋白的亚细胞分布。未成熟角化包膜在新生小鼠表皮中的比例高于杂合子和野生型小鼠，且包膜表面积较大。这与胚胎发育过程中屏障获得的轻微延迟有关。我们的结论是，虽然包膜蛋白是角化的包膜组装在其上的支架的一部分，但它对包膜的形成或表皮屏障功能并不是必需的。
Envoplakin, a member of the plakin family of cytoskeletal linker proteins, is localized in desmosomes of stratified epithelial cells and is a component of the epidermal cornified envelope. Gene targeting in mouse embryonic stem cells was used to generate a null allele of envoplakin. No envoplakin transcripts from the targeted allele could be detected in the skin of newborn mice. Mice homozygous for the targeted allele were born in the normal Mendelian ratio and were fertile. They did not develop any discernible pathological phenotype up to the age of I year. The ultrastructural appearance of cornified envelopes from adult epidermis was indistinguishable between wild-type and knockout mice, and there was no evidence that the absence of envoplakin affected the subcellular distribution of periplakin or desmoplakin, two other plakins found in desmosomes. The proportion of immature cornified envelopes in the epidermis of newborn mice was greater in envoplakin-null animals than in heterozygous littermates or wild-type mice, and the envelopes had a larger surface area. This correlated with a slight delay in barrier acquisition during embryonic development. We conclude that although envoplakin is part of the scaffolding on which the cornified envelope is assembled, it is not essential for envelope formation or epidermal barrier function.