Alpy F, Jivkov I, Sorokin L, Klein A, Arnold C, Huss Y, Kedinger M, Simon-Assmann P, Lefebvre O
Inserm, U682 Strasbourg, F67200, Development and Physiopathology of the Intestine and Pancreas, University Louis Pasteur, Strasbourg, France.
Genesis. 2005 Oct;43(2):59-70. doi: 10.1002/gene.20154.
Laminins are heterotrimeric glycoproteins of the basement membranes. Laminin 1 (alpha1, beta1, gamma1) is the major laminin expressed during early mouse embryogenesis. To gain access to the physiological function of laminin alpha1 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 alpha1 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 Lama1 gene in various organs.
层粘连蛋白是基底膜的异源三聚体糖蛋白。层粘连蛋白1（α1、β1、γ1）是小鼠胚胎早期发育过程中表达的主要层粘连蛋白。为了探究层粘连蛋白α1链的生理功能，我们利用cre/loxP系统构建了其编码基因（Lama1）的条件性无效等位基因。携带floxed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，以产生Lama1基因缺陷小鼠（Lama1(Delta/Delta)）。Lama1(Delta/Delta)胚胎在胚胎第6.5天之后的植入后早期死亡。它们缺乏赖歇特膜，这是一种胚外基底膜，其中层粘连蛋白α1通常高度表达。同时，Lama1(Delta/Delta)胚胎表现出：1）分别伴有细胞角蛋白19和GATA4表达改变的壁层和脏层内胚层分化缺陷，以及2）细胞凋亡的诱导。这个新的小鼠模型特别引人关注，因为它将允许在各个器官中对Lama1基因进行时间和组织特异性失活。
