Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice.

Kwee L, Baldwin HS, Shen HM, Stewart CL, Buck C, Buck CA, Labow MA
Development. 1995 121 (2): 489-503

PMID: 7539357

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.

MeSH Terms (18)

Allantois Animals Antigens, CD Cardiovascular System Cell Adhesion Molecules Chorion Fetal Death Gene Expression Genotype Heart Immunohistochemistry Integrin alpha4 Mice Mice, Mutant Strains Placenta Placentation Receptors, Lymphocyte Homing Vascular Cell Adhesion Molecule-1

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