PT - JOURNAL ARTICLE AU - Kwee, L. AU - Baldwin, H.S. AU - Shen, H.M. AU - Stewart, C.L. AU - Buck, C. AU - Buck, C.A. AU - Labow, M.A. TI - Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice DP - 1995 Feb 01 TA - Development PG - 489--503 VI - 121 IP - 2 4099 - http://dev.biologists.org/content/121/2/489.short 4100 - http://dev.biologists.org/content/121/2/489.full SO - Development1995 Feb 01; 121 AB - VCAM-1 is a cytokine-inducible cell surface protein capable of mediating adhesion to leukocytes expressing alpha 4 integrins. Mice deficient in VCAM-1 expression were produced by targeted homologous recombination in ES cells. VCAM-1-deficient embryos were not viable and exhibited either of two distinct phenotypes. Approximately half of the embryos died before embryonic day 11.5 and exhibited a severe defect in placental development in which the allantois failed to fuse with the chorion. The remaining VCAM-1-deficient embryos survived to embryonic day 11.5-12.5 and displayed several abnormalities in their developing hearts including a reduction of the compact layer of the ventricular myocardium and intraventricular septum. The hearts also contained significant amounts of blood in the pericardial space and lacked an epicardium. alpha 4 and VCAM-1 were found to be expressed in wild-type embryos in a reciprocal fashion in the chorion and allantois and in the epicardium and the underlying myocardium, although VCAM-1 was expressed in the intraventricular septum in the absence of adjacent alpha 4-expressing cells. These data suggest important roles for VCAM-1 and alpha 4 in the development of the placenta and the heart.