Gawlik Kinga I, Durbeej Madeleine
Department of Experimental Medical Science, Muscle Biology Unit, Lund University, Sweden.
Sci Rep. 2015 Sep 10;5:13916. doi: 10.1038/srep13916.
Laminin-211 is a major constituent of the skeletal muscle basement membrane, exerting its biological functions by binding to cell surface receptors integrin α7β1 and dystroglycan (the latter is part of the dystrophin-glycoprotein complex). The importance of these molecules for normal muscle function is underscored by the fact that their respective deficiency leads to different forms of muscular dystrophy with different severity in humans and animal models. We recently demonstrated that laminin α2 chain and members of the dystrophin-glycoprotein complex have overlapping but non-redundant roles despite being part of the same adhesion complex. To analyse whether laminin-211 and integrin α7 subunit have non-redundant functions we generated mice deficient in laminin α2 chain and integrin α7 subunit (dy(3K)/itga7). We show that lack of both molecules did not exacerbate the severe phenotype of laminin α2-chain deficient animals. They displayed the same weight, survival and dystrophic pattern of muscle biopsy, with similar degree of inflammation and fibrosis. These data suggest that laminin-211 and integrin α7β1 have intersecting roles in skeletal muscle.
层粘连蛋白-211是骨骼肌基底膜的主要成分，通过与细胞表面受体整合素α7β1和营养不良聚糖（后者是肌营养不良蛋白-糖蛋白复合物的一部分）结合来发挥其生物学功能。这些分子对正常肌肉功能的重要性体现在，在人类和动物模型中，它们各自的缺陷会导致不同形式、不同严重程度的肌营养不良症。我们最近证明，尽管层粘连蛋白α2链和肌营养不良蛋白-糖蛋白复合物的成员属于同一黏附复合物，但它们具有重叠但非冗余的作用。为了分析层粘连蛋白-211和整合素α7亚基是否具有非冗余功能，我们培育出了层粘连蛋白α2链和整合素α7亚基缺陷的小鼠（dy(3K)/itga7）。我们发现，同时缺乏这两种分子并不会加剧层粘连蛋白α2链缺陷动物的严重表型。它们的体重、存活率以及肌肉活检的营养不良模式相同，炎症和纤维化程度也相似。这些数据表明，层粘连蛋白-211和整合素α7β1在骨骼肌中具有交叉作用。
