Consequences of lack of beta 1 integrin gene expression in mice.
beta 1 integrins are cell-surface receptors that mediate cell-cell and cell-matrix interactions. We have generated a null mutation in the gene for the beta 1 integrin subunit in mice and embryonic stem (ES) cells. Heterozygous mice are indistinguishable from normal littermates. Homozygous null embryos develop normally to the blastocyst stage, implant, and invade the uterine basement membrane but die shortly thereafter. Using beta 1 integrin-deficient ES cells we have established chimeric embryos and adult mice. Analysis of the chimeric embryos demonstrated the presence of beta 1 integrin-deficient cells in all germ layers indicating that beta 1-null cells can differentiate and migrate in a context of normal tissue. When evaluated at embryonic day 9.5 (E9.5), embryos with a beta 1-null cell contribution below 25% were developing normally, whereas embryos with a contribution above this threshold were distorted and showed abnormal morphogenesis. In adult chimeric mice beta 1 integrin-deficient cells failed to colonize liver and spleen but were found in all other tissues analyzed at levels from 2%-25%. Immunostaining of chimeric mice showed that in cardiac muscle, there were small, scattered patches of myocytes that were beta 1-null. In contrast, many myotubes showed some beta 1-null contribution as a result of fusion between wild-type and mutant myoblasts to form mixed myotubes. The adult chimeric brain contained beta 1-null cells in all regions analyzed. Also, tissues derived from the neural crest contained beta 1 integrin-deficient cells indicating that migration of neuronal cells as well as neural crest cells can occur in the absence of beta 1 integrins.
Fässler
R
R
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Meyer
M
M
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology; D002465:Cell Movement; D002678:Chimera; D004622:Embryo, Mammalian / Q000473:pathology*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005804:Genes, Lethal / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D019012:Integrin beta1; D016023:Integrins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009432:Neural Crest / Q000196:embryology; D011247:Pregnancy; D011995:Recombination, Genetic; D013234:Stem Cells
D019012:Integrin beta1; D016023:Integrins