Role for the α7β1 integrin in vascular development and integrity

The alpha 7 beta 1 integrin is a laminin receptor that has been implicated in muscle disease and the development of neuromuscular and myotendinous junctions. Studies have shown the alpha 7 beta 1 integrin is also expressed in nonskeletal muscle tissues. To identify the expression pattern of the alpha 7 integrin in these tissues during embryonic development, alpha 7 integrin chain knockout mice were generated by a LacZ knockin strategy. In these mice, expression from the alpha 7 promoter is reported by beta-galactosidase. From embryonic day (ED) 11.5 to ED14.5, beta-galactosidase was detected in the developing central and peripheral nervous systems and vasculature. The loss of the alpha 7 integrin gene resulted in partial embryonic lethality. Several alpha 7 null embryos were identified with cerebrovascular hemorrhages and showed reduced vascular smooth muscle cells and cerebral vascularization. The alpha 7 null mice that survived to birth exhibited vascular smooth muscle defects, including hyperplasia and hypertrophy. In addition, altered expression of alpha 5 and alpha 6B integrin chains was detected in the cerebral arteries of alpha 7 null mice, which may contribute to the vascular phenotype. Our results demonstrate for the first time that the alpha 7 beta 1 integrin is important for the recruitment or survival of cerebral vascular smooth muscle cells and that this integrin plays an important role in vascular development and integrity. (c) 2005 Wiley-Liss, Inc.