Embryonic heart and skin defects in mice lacking plakoglobin
Embryonic heart and skin defects in mice lacking plakoglobin
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DOI：
10.1006/dbio.1996.0346
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发表时间：
1996-12-15
影响因子：
2.7
通讯作者：
Kemler, R
中科院分区：
文献类型：
--
作者：
Bierkamp, C;McLaughlin, KJ;Kemler, R
白蛋白是黏附连接中桥粒斑块和钙粘附素-连环蛋白细胞黏附复合体的唯一共同成分，它与脊椎动物β-连环蛋白和果蝇蝉蛋白高度同源，并可能像这些蛋白质一样参与信号通路。为了分析白蛋白在小鼠发育中的作用，我们在胚胎干细胞中通过同源重组使白蛋白基因失活，并产生了转基因小鼠，白蛋白零突变胚胎从胚胎第10.5天开始死亡，原因是严重的心脏缺陷。一些突变胚胎进一步发育，特别是在C57BL/6的遗传背景下，并在出生前后死亡，可能是由于心脏功能障碍，并伴有皮肤起泡和角膜下棘层松解。超微结构分析显示，桥粒数量明显减少，结构发生改变。因此，利用反向遗传学，我们证明了白蛋白是桥粒功能的基本结构成分，白蛋白缺陷小鼠的皮肤表型使人联想到人类水泡病，表皮松解性角化过度。(C)1996年学术出版社。
Plakoglobin is the only component common to both the desmosomal plaque and the cadherin-catenin cell adhesion complex in the adherens junction, It is highly homologous to vertebrate beta-catenin and to Drosophila armadillo protein and may - like these proteins - be also involved in signaling pathways. To analyze the role of plakoglobin during mouse development we inactivated the plakoglobin gene by homologous recombination in embryonic stem cells and generated transgenic mice, Plakoglobin null-mutant embryos died from Embryonic Day 10.5 onward, due to severe heart defects. Some mutant embryos developed further, especially on a C57BL/6 genetic background, and died around birth, presumably due to cardiac dysfunction, and with skin blistering and subcorneal acantholysis. Ultrastructural analysis revealed that here desmosomes were greatly reduced in number and structurally altered. Thus, using reversed genetics we demonstrate that plakoglobin is an essential structural component for desmosome function, The skin phenotype in plakoglobin-deficient mice is reminiscent of the human blistering disease, epidermolytic hyperkeratosis. (C) 1996 Academic Press, Inc.