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Additional sex combs-like family genes are required for normal cardiovascular development.

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      Abstract

      Congenital heart disease (CHD) is the most common birth defect. However, the majority of CHD cases have unknown etiology. Here we report the identification of ASXL2 and ASXL1, two homologous chromatin factors, as novel regulators of heart development. Asxl2(-/-) fetuses have reduced body weight and display congenital heart malformations including thickened compact myocardium in the left ventricle, membranous ventricular septal defect, and atrioventricular valval stenosis. Although most Asxl2(-/-) animals survive to term, the neonates have patent ductus arteriosus and consequent lung hemorrhage and die soon after birth. Asxl1(-/-) fetuses have reduced body weight and display cleft palate, anophthalmia as well as ventricular septal defects and a failure in lung maturation. From these results, we conclude that normal heart development requires both ASXL proteins. In particular, ASXL2 plays an important role in heart morphogenesis and the transition from fetal to postnatal circulation.

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      Affiliations
      [1 ] Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois.
      Journal
      Genesis
      Genesis (New York, N.Y. : 2000)
      Wiley-Blackwell
      1526-968X
      1526-954X
      Jul 2014
      : 52
      : 7
      24860998
      10.1002/dvg.22793

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