TGF-beta receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis

TGF-beta signaling is mediated through two types of serine/threonin kinase-containing receptors, type I (TGF-beta RI) and type II (TGF-beta RII), which form a heteromeric complex. In this signaling complex, ligand binding TGF-beta RII phosphorylates and thereby activates the TGF-beta RI to signal downstream pathways. To determine the role of TGF-beta RII in embryogenesis, we have generated a TGF-beta RII gene (Tgfbr2) knockout mouse line. The heterozygous Tgfbr2 knockout mice are developmentally normal. The homozygous Tgfbr2 mutation causes defects in the yolk sac hematopoiesis and vasculogenesis, resulting in an embryonic lethality around 10.5 days of gestation. This phenotype is indistinguishable from the previously reported embryonic lethality by the homozygous TGF-beta 1 gene (Tgfb1) null mutation. In addition, we have generated chimeric mice using a Tgfbr2 (-/-) embryonic stem cell line. Some chimeric mice showed several types of congenital anomalies, suggesting that TGF-beta RII is important for normal development in a variety of organs. (C) 1996 Academic Press, Inc.