title: Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation.
abstract: Vascular cell adhesion molecule-1 (VCAM-1) is expressed on vascular endothelium in a variety of inflammatory conditions and mediates leukocyte recruitment from blood into tissues. In this study we report a novel role for VCAM-1 in the formation of the umbilical cord and placenta during development. The murine VCAM1 gene was disrupted by targeted homologous recombination, and a distinct phenotype was found in VCAM-1-deficient embryos. At 8.5 days of gestation, the allantois failed to fuse to the chorion, resulting in abnormal placental development and embryonic death within 1-3 days. In addition, a role for VCAM-1 in early placental formation after chorioallantoic fusion was observed. In a minority of VCAM-1-deficient embryos, the allantois was able to fuse with the chorion, but the allantoic mesoderm was abnormally distributed over the chorionic surface. A small number of VCAM-1-deficient embryos survived, presumably by circumventing the placentation defects. They became viable and fertile adult mice with lack of VCAM-1 expression, normal organs, and an elevated number of circulating blood mononuclear leukocytes.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: G C
authors.initials: GC
authors.lastname: Gurtner
authors.forename: V
authors.initials: V
authors.lastname: Davis
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: M J
authors.initials: MJ
authors.lastname: McCoy
authors.forename: A
authors.initials: A
authors.lastname: Sharpe
authors.forename: M I
authors.initials: MI
authors.lastname: Cybulsky
mesh_terms: D000482:Allantois / Q000196:embryology*; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000302:isolation & purification; D002823:Chorion / Q000196:embryology*; D005260:Female; D006330:Heart Defects, Congenital / Q000196:embryology; D007150:Immunohistochemistry; D039441:Integrin alpha4; D016023:Integrins / Q000302:isolation & purification; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010920:Placenta / Q000002:abnormalities* / Q000196:embryology; D010929:Placentation / Q000235:genetics; D011247:Pregnancy; D014018:Tissue Distribution; D014470:Umbilical Cord / Q000002:abnormalities* / Q000196:embryology; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015815:Cell Adhesion Molecules; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4