Absence of TGFβ Signaling in Embryonic Vascular Smooth Muscle Leads to Reduced Lysyl Oxidase Expression, Impaired Elastogenesis, and Aneurysm

To address the requirement for TGF beta signaling in the formation and maintenance of the vascular matrix, we employed lineage-specific mutation of the type II TGF beta receptor gene (Tgfbr2) in vascular smooth muscle precursors in mice. In both neural crest- and mesoderm-derived smooth muscle, absence of TGF beta receptor function resulted in a poorly organized vascular elastic matrix in late-stage embryos which was prone to dilation and aneurysm. This defect represents a failure to initiate formation of the elastic matrix, rather than a failure to maintain a preexisting matrix. In mutant tissue, lysyl oxidase expression was substantially reduced, which may contribute to the observed pathology. genesis 47:115-121, 2009. (C) 2009 Wiley-Liss, Inc.