Deletion of integrin alpha 1 by homologous recombination permits normal murine development but gives rise to a specific deficit in cell adhesion.
Integrin alpha 1 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 alpha 1 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 alpha 1 beta 1 is not required for binding to collagen I and implicates a third receptor, possibly integrin alpha 3 beta 1, in collagen I binding.
Gardner
H
H
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA.
Kreidberg
J
J
Koteliansky
V
V
Jaenisch
R
R
D000483:Alleles; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D002678:Chimera; D003094:Collagen / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D005298:Fertility; D005347:Fibroblasts / Q000166:cytology; D017353:Gene Deletion; D018390:Gene Targeting; D039423:Integrin alpha1; D016023:Integrins / Q000502:physiology; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D038981:Receptors, Collagen; D011995:Recombination, Genetic; D014162:Transfection; D014599:Uterus / Q000166:cytology
D015703:Antigens, CD; D039423:Integrin alpha1; D016023:Integrins; D007797:Laminin; D038981:Receptors, Collagen; D003094:Collagen