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

Abstract

TGF-β signaling is mediated through two types of serine/threonin kinase-containing receptors, type I (TGF-βRI) and type II (TGF-βRII), which form a heteromeric complex. In this signaling complex, ligand binding TGF-βRII phosphorylates and thereby activates the TGF-βRI to signal downstream pathways. To determine the role of TGF-βRII in embryogenesis, we have generated a TGF-βRII 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-β1 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-βRII is important for normal development in a variety of organs.