E-cadherin is a survival factor for the lactating mouse mammary gland
E-cadherin is a survival factor for the lactating mouse mammary gland
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DOI：
10.1016/s0925-4773(02)00090-4
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发表时间：
2002-07-01
影响因子：
2.6
通讯作者：
Kemler, R
中科院分区：
文献类型：
--
作者：
Boussadia, O;Kutsch, S;Kemler, R
钙离子依赖性细胞粘附分子E-cadherin在整个小鼠发育过程中和成体组织中表达。经典的基因靶向已经证明E-钙粘蛋白缺陷的胚胎在胚泡阶段死亡。为了研究E-cadherin在器官发生中的作用，采用噬菌体P1重组酶Cre/loxP系统进行了条件性基因失活。产生在E-钙粘蛋白（Cdh 1）基因的两个等位基因中具有纯合loxP位点的小鼠，并将这些小鼠与具有Cre重组酶的转基因小鼠杂交，所述Cre重组酶在病毒诱导型MMTV启动子的控制下。这导致在乳腺的分化肺泡上皮细胞中的E-钙粘蛋白基因的缺失。突变体乳腺发育正常，怀孕16-18天，但分娩时表现出显着的表型。乳蛋白质的生产急剧减少，成年突变母亲无法喂养她们的后代。因此，E-钙粘蛋白的缺乏影响了泌乳期乳腺的终末分化程序。与这一发现相一致，催乳素依赖性激活的转录因子Stat 5a的启动，但不保持在突变体腺体。相反，没有E-cadherin大量细胞死亡观察分娩和突变乳腺在这个阶段类似的退化的腺体通常看到断奶后。这些结果表明，在分化的肺泡上皮细胞的功能的E-钙粘蛋白的重要作用。在缺乏E-钙粘蛋白的突变腺体中未检测到肿瘤。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
The Ca++-dependent cell adhesion molecule E-cadherin is expressed throughout mouse development and in adult tissues. Classical gene targeting has demonstrated that E-cadherin-deficient embryos die at the blastocyst stage. To study the involvement of E-cadherin in organogenesis, a conditional gene inactivation scheme was under-taken using the bacteriophage P1 recombinase Cre/loxP system. Mice with homozygous loxP sites in both alleles of the E-cadherin (Cdh1) gene were generated and these mice were crossed with transgenic mice with the Cre recombinase under the control of the hormone-inducible MMTV promoter. This resulted in deletion of the E-cadherin gene in the differentiating alveolar epithelial cells of the mammary gland. The mutant mammary gland developed normally up to 16-18 days of pregnancy but exhibited a dramatic phenotype around parturition. The production of milk proteins was so drastically reduced that adult mutant mothers could not suckle their offspring. Thus, the lack of E-cadherin affected the terminal differentiation program of the lactating mammary gland. In concordance with this finding, the prolactin-dependent activation of the transcription factor Stat5a was initiated but not maintained in the mutant gland. Instead, without E-cadherin massive cell death was observed at parturition and the mutant mammary gland at this stage resembled that of the involuted gland normally seen after weaning. These results demonstrate an essential role for E-cadherin in the function of differentiated alveolar epithelial cells. No tumors were detected in mutant glands lacking E-cadherin. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.