Feltri M Laura, Graus Porta Diana, Previtali Stefano C, Nodari Alessandro, Migliavacca Barbara, Cassetti Arianna, Littlewood-Evans Amanda, Reichardt Louis F, Messing Albee, Quattrini Angelo, Mueller Ulrich, Wrabetz Lawrence
Department of Biological and Technological Research, San Raffaele Scientific Institute, 20132 Milan, Italy.
J Cell Biol. 2002 Jan 7;156(1):199-209. doi: 10.1083/jcb.200109021. Epub 2002 Jan 3.
In dystrophic mice, a model of merosin-deficient congenital muscular dystrophy, laminin-2 mutations produce peripheral nerve dysmyelination and render Schwann cells unable to sort bundles of axons. The laminin receptor and the mechanism through which dysmyelination and impaired sorting occur are unknown. We describe mice in which Schwann cell-specific disruption of beta1 integrin, a component of laminin receptors, causes a severe neuropathy with impaired radial sorting of axons. beta 1-null Schwann cells populate nerves, proliferate, and survive normally, but do not extend or maintain normal processes around axons. Interestingly, some Schwann cells surpass this problem to form normal myelin, possibly due to the presence of other laminin receptors such as dystroglycan and alpha 6 beta 4 integrin. These data suggest that beta 1 integrin links laminin in the basal lamina to the cytoskeleton in order for Schwann cells to ensheath axons, and alteration of this linkage contributes to the peripheral neuropathy of congenital muscular dystrophy.
在肌营养不良小鼠（一种缺乏merosin的先天性肌营养不良模型）中，层粘连蛋白-2突变会导致周围神经脱髓鞘，并使施万细胞无法对轴突束进行分类。层粘连蛋白受体以及脱髓鞘和分类受损发生的机制尚不清楚。我们描述了这样的小鼠，其中施万细胞特异性破坏层粘连蛋白受体的一个组成部分β1整合素，会导致严重的神经病变，轴突的放射状分类受损。β1基因缺失的施万细胞在神经中聚集、增殖并正常存活，但不会在轴突周围延伸或维持正常的突起。有趣的是，一些施万细胞克服了这个问题形成了正常的髓鞘，这可能是由于存在其他层粘连蛋白受体，如肌营养不良聚糖和α6β4整合素。这些数据表明，β1整合素将基膜中的层粘连蛋白与细胞骨架相连，以便施万细胞包裹轴突，而这种连接的改变会导致先天性肌营养不良的周围神经病变。
