The essential role of Cited2, a negative regulator for HIF-1α, in heart development and neurulation

• DOI: 10.1073/pnas.162371799
• Publication Date: 2002-09-30T16:42:53Z
• Authors: Zhan Yin; Jennifer Haynie; Xiaoming Yang; Baoguang Han; Songsak Kiatchoos...; Joseph Restivo; Saying Yuan; Nanduri R. Prabhakar; Karl Herrup; Ronald A. Conlon; Brian D. Hoit; Michiko Watanabe; Yu-Chung Yang
• Keywords: Heart development; Hypoxia

Cited2 is a cAMP-responsive element-binding protein (CBP)/p300 interacting transcriptional modulator and proposed negative regulator for hypoxia-inducible factor (HIF)-1α through its competitive binding with HIF-1α to CBP/p300. Disruption of the gene encoding embryonic lethal because defects in development heart neural tube. Morphological Doppler echocardiographic analyses −/− embryos reveal severe cardiovascular abnormalities, including pulmonic arterial stenosis ventricular septal accompanied by high peak outflow velocities, features human congenital cardiac defect termed tetralogy Fallot. The mRNA levels several HIF-1α-responsive genes, such as vascular endothelial growth (VEGF), Glut1, phosphoglycerate kinase 1, increased hearts. increase VEGF significant, closely resemble major observed transgenic embryos. Finally, compared wild-type, cultured fibroblasts from demonstrate an enhanced expression genes under hypoxic conditions. These observations suggest that functional loss responsible tube development, part modulation HIF-1 activities absence Cited2. findings indispensable regulatory during prenatal development.