Sackler School for Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, United States.
Matrix Biol. 2012 Mar;31(2):120-34. doi: 10.1016/j.matbio.2011.12.002. Epub 2011 Dec 24.
Laminins are heterotrimeric extracellular glycoproteins found in, but not confined to, basement membranes (BMs). They are important components in formation of the molecular networks of BMs as well as in cell polarity, cell differentiation and tissue morphogenesis. Each laminin is composed by an α, a β and a γ chain. Previous studies have shown that the γ3 chain is partnered with either the β1 chain (in placenta) or β2 chain (in the CNS) (Libby et al., 2000). Several studies, including our own, suggested that the γ3 chain is expressed in both apical and basal compartments (Koch et al., 1999; Gersdorff et al., 2005; Yan and Cheng, 2006). This study investigates the expression pattern of the γ3 chain in mouse. We developed three new γ3-reactive antibodies, and we show that the γ3 chain is present in BMs. The distribution pattern is considerably more restricted than that of the γ1 chain and within any tissue there is differential deposition into BM compartments. This is particularly true in the retina and brain, where γ3 is uniquely expressed in a subset of the vascular basement membranes and the pial surface. We used conventional genetic ablation techniques to remove the γ3 chain in mice; unlike other laminin null mice (α5, β2, γ1 nulls), these mice live a normal lifespan and have only minor abnormalities, the most striking of which are ectopic granule cells in the cerebellum and an apparent increase in capillary branching in the outer retina. These data support the suggestion that the γ3 chain is deposited in BMs and contributes some unique properties to their function, particularly in the nervous system.
层粘连蛋白是异三聚体细胞外糖蛋白，存在于但不限于基底膜 (BMs) 中。它们是形成 BMs 分子网络以及细胞极性、细胞分化和组织形态发生的重要组成部分。每个层粘连蛋白由一个α、一个β和一个γ链组成。先前的研究表明，γ3 链与β1 链（在胎盘）或β2 链（在中枢神经系统）结合（Libby 等人，2000）。包括我们自己在内的几项研究表明，γ3 链在顶区和基底区都有表达（Koch 等人，1999；Gersdorff 等人，2005；Yan 和 Cheng，2006）。本研究调查了 γ3 链在小鼠中的表达模式。我们开发了三种新的γ3 反应性抗体，并表明 γ3 链存在于 BMs 中。分布模式比 γ1 链更为局限，并且在任何组织中，都有差异地沉积到 BM 隔室中。这在视网膜和大脑中尤为明显，其中 γ3 仅在血管基底膜和软脑膜的一部分中表达。我们使用传统的遗传消融技术在小鼠中去除 γ3 链；与其他层粘连蛋白缺失小鼠（α5、β2、γ1 缺失）不同，这些小鼠的寿命正常，只有轻微的异常，最明显的是小脑的异位颗粒细胞和外视网膜毛细血管分支的明显增加。这些数据支持这样的假设，即 γ3 链沉积在 BMs 中，并为其功能提供一些独特的特性，特别是在神经系统中。
