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Background  Patent ductus arteriosus (PDA) is one of the most common forms of congenital heart disease. Mutations in transcription factor  TFAP2B  cause Char syndrome, a human disorder characterized by PDA, facial dysmorphysm and hand anomalies. Animal research data are needed to understand the mechanisms. The aim of our study was to elucidate the pathogenesis of Char syndrome at the molecular level.    Methodology/Principal Findings  Gene expression of  Tfap2b  during mouse development was studied, and newborns of Tfap2b-deficient mice were examined to identify phenotypes. Gel shift assays had been carried out to search for Tfap2 downstream genes. Promoters of candidate genes were cloned into a reporter construct and used to demonstrate their regulation by Tfap2b in cell transfection. In situ hybridizations showed that the murine transcription factor  Tfap2b  was expressed during the entire development of mouse ductus arteriosus. Histological examination of ductus arteriosus from  Tfap2b  knockout mice 6 hours after birth revealed that they were not closed. Consequently, the lungs of  Tfap2b   −/−  mice demonstrated progressive congestion of the pulmonary capillaries, which was postulated to result secondarily from PDA. In addition,  Tfap2b  was expressed in the limb buds, particularly in the posterior limb field during development. Lack of  Tfap2b  resulted in bilateral postaxial accessory digits. Further study indicated that expressions of bone morphogenetic protein ( Bmp ) genes, which are reported to be involved in the limb patterning and ductal development, were altered in limb buds of Tfap2b-deficient embryos, due to direct control of  Bmp2  and  Bmp4  promoter activity by Tfap2b.    Conclusions/Significance  Tfap2b plays important roles in the development of mouse ductus arteriosus and limb patterning. Loss of Tfap2b results in altered Bmp expression that may cause the heart-limb defects observed in  Tfap2b  mouse mutants and Char syndrome patients. The Tfap2b knockout mouse may add to the very limited available animal models of PDA.

A Heart-Hand Syndrome Gene: Tfap2b Plays a Critical Role in the Development and Remodeling of Mouse Ductus Arteriosus and Limb Patterning