Deletion of integrin α1 by homologous recombination permits normal murine development but gives rise to a specific deficit in cell adhesion

Abstract

Integrin α1 is a receptor for laminin and collagen which is expressed widely and dynamically in embryogenesis and has been implicated in various developmental processes including establishment of the placenta and formation of the central and peripheral nervous system. In the adult it is the sole collagen receptor in smooth muscle and liver and is thought to be important for the stability of these tissues. We have generated a null allele of the α1 gene in the germline of mice by homologous recombination in embryonic stem cells. Mice homozygous for the mutation are viable and fertile and have no overt phenotype, demonstrating that the molecule is not required for development. Embryonic fibroblasts derived from mutant animals are unable to spread on or migrate into substrata of collagen IV and are deficient in spreading on and migrating into laminin. further in vitro analysis of cell spreading and migration suggests that α1β1 is not required for binding to collagen I and implicates a third receptor, possibly integrin α3β1, in collagen I binding.