In this report, we demonstrate that conditional pRb loss in the Tie2 lineage is sufficient to cause age-dependent aortic valve thickening, ECM disorganization and regurgitation reminiscent of human fibrotic valvular disease or aortic valve sclerosis, a stage that precedes frank CAVD [3]. This evidence concerns the gene TEK and congenital bilateral aplasia of vas deferens from CFTR mutation.