Generation of a conditionally null allele of the laminin α1 gene
Generation of a conditionally null allele of the laminin α1 gene
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DOI：
10.1002/gene.20154
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发表时间：
2005-10-01
期刊：
影响因子：
1.5
通讯作者：
Lefebvre, O
中科院分区：
文献类型：
--
作者：
Alpy, F;Jivkov, I;Lefebvre, O
层粘连蛋白是基底膜的异三聚体糖蛋白。层粘连蛋白1 （α 1, β 1, γ 1）是小鼠胚胎早期表达的主要层粘连蛋白。为了了解层粘连蛋白α 1链的生理功能，我们利用cre/loxP系统开发了其编码基因（Lama1）的条件空等位基因。携带flox等位基因的小鼠（Lama1(flox/flox)）没有明显的表型。将Lama1（flox/flox）小鼠与转基因缺失小鼠（CMV-Cre）杂交，生成Lama1缺陷小鼠（Lama1(Delta/Delta)）。Lama1（Delta/Delta）胚在胚期6.5天后的早期植入期死亡。它们缺乏赖克特膜，这是一种胚外基底膜，层粘连蛋白通常在其中高度表达。同样，Lama1（Delta/Delta）胚胎表现出1)壁层和内脏内胚层分化缺陷，分别表现为细胞角蛋白19和GATA4的表达改变，2)诱导凋亡。这种新的小鼠模型是特别有趣的，因为它将允许在不同器官的Lamal基因的时间和组织特异性失活。创世纪43:59-70,2005。(c) 2005 Wiley-Liss, Inc。
Laminins are heterotrimeric glycoproteins of the basement membranes. Laminin 1 (alpha 1, beta 1, gamma 1) is the major laminin expressed during early mouse embryogenesis. To gain access, to the physiological function of laminin alpha 1 chain, we developed a conditionally null allele of its encoding gene (Lama1) using the cre/loxP system. Floxed-allele-carrying mice (Lama1(flox/flox)) display no overt phenotype. Lama1(flox/flox) mice were crossed with transgenic deleter mice (CMV-Cre) to generate Lama1-deficient mice (Lama1(Delta/Delta)). Lama1(Delta/Delta) embryos die during the early postimplantation period after embryonic day 6.5. They lack Reichert's membrane, an extraembryonic basement membrane in which laminin all is normally highly expressed. In parallel, Lama1(Delta/Delta) embryos display 1) parietal and visceral endoderm differentiation defects with altered expression of cytokeratin 19 and GATA4, respectively, and 2) an induction of apoptosis. This new mouse model is of particular interest as it will allow time- and tissue-specific inactivation of the Lamal gene in various organs. genesis 43:59-70, 2005. (c) 2005 Wiley-Liss, Inc.