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Vol. 18, Issue 3, 943-952, March 2007

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Loss of Vav2 Proto-Oncogene Causes Tachycardia and Cardiovascular Disease in Mice

Vincent Sauzeau^*, Mirjana Jerkic, José M. López-Novoa, and Xosé R. Bustelo^*

*Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer and Departamento de Fisiología y Farmacología, Consejo Superior de Investigaciones Científicas, University of Salamanca, E-37007 Salamanca, Spain

Submitted October 2, 2006; Revised November 27, 2006; Accepted December 21, 2006
Monitoring Editor: J. Silvio Gutkind

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.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Xosé R. Bustelo (xbustelo{at}usal.es)

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