Role for the alpha7beta1 integrin in vascular development and integrity.
The alpha7beta1 integrin is a laminin receptor that has been implicated in muscle disease and the development of neuromuscular and myotendinous junctions. Studies have shown the alpha7beta1 integrin is also expressed in nonskeletal muscle tissues. To identify the expression pattern of the alpha7 integrin in these tissues during embryonic development, alpha7 integrin chain knockout mice were generated by a LacZ knockin strategy. In these mice, expression from the alpha7 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 alpha7 integrin gene resulted in partial embryonic lethality. Several alpha7 null embryos were identified with cerebrovascular hemorrhages and showed reduced vascular smooth muscle cells and cerebral vascularization. The alpha7 null mice that survived to birth exhibited vascular smooth muscle defects, including hyperplasia and hypertrophy. In addition, altered expression of alpha5 and alpha6B integrin chains was detected in the cerebral arteries of alpha7 null mice, which may contribute to the vascular phenotype. Our results demonstrate for the first time that the alpha7beta1 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.