Loss of Vav2 proto-oncogene causes tachycardia and cardiovascular disease in mice.
The Vav family is a group of signal transduction molecules that activate Rho/Rac GTPases during cell signaling. Experiments using knockout mice have indicated that the three Vav proteins present in mammals (Vav1, Vav2, and Vav3) are essential for proper signaling responses in hematopoietic cells. However, Vav2 and Vav3 are also highly expressed in nonhematopoietic tissues, suggesting that they may have additional functions outside blood cells. Here, we report that this is the case for Vav2, because the disruption of its locus in mice causes tachycardia, hypertension, and defects in the heart, arterial walls, and kidneys. We also provide physiological and pharmacological evidence demonstrating that the hypertensive condition of Vav2-deficient mice is due to a chronic stimulation of the renin/angiotensin II and sympathetic nervous systems. Together, these results indicate that Vav2 plays crucial roles in the maintenance of cardiovascular homeostasis in mice.
Sauzeau
Vincent
V
Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, University of Salamanca, E-37007 Salamanca, Spain.
Jerkic
Mirjana
M
López-Novoa
José M
JM
Bustelo
Xosé R
XR
D000311:Adrenal Glands / Q000648:ultrastructure; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001011:Aorta / Q000473:pathology; D016232:Endothelins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency; D006352:Heart Ventricles / Q000473:pathology; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000002:abnormalities / Q000503:physiopathology; D007677:Kidney Function Tests; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D051567:Proto-Oncogene Proteins c-vav / Q000172:deficiency* / Q000378:metabolism*; D012084:Renin-Angiotensin System; D013564:Sympathetic Nervous System / Q000378:metabolism; D013610:Tachycardia / Q000473:pathology*; D014667:Vasopressins / Q000097:blood
D016232:Endothelins; D020662:Guanine Nucleotide Exchange Factors; D051567:Proto-Oncogene Proteins c-vav; C490565:Vav2 protein, mouse; C496622:Vav3 protein, mouse; D014667:Vasopressins; D000450:Aldosterone