Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice.
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.
Kwee
L
L
Department of Biotechnology, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110-1199, USA.
Baldwin
H S
HS
Shen
H M
HM
Stewart
C L
CL
Buck
C
C
Buck
C A
CA
Labow
M A
MA
D000482:Allantois / Q000098:blood supply / Q000196:embryology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D002319:Cardiovascular System / Q000196:embryology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002823:Chorion; D005313:Fetal Death; D015870:Gene Expression; D005838:Genotype; D006321:Heart / Q000196:embryology; D007150:Immunohistochemistry; D039441:Integrin alpha4; D051379:Mice; D008817:Mice, Mutant Strains; D010920:Placenta / Q000098:blood supply*; D010929:Placentation; D016201:Receptors, Lymphocyte Homing / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4