Strain dependency of TGF beta 1 function during embryogenesis

There is incomplete penetrance to Tgfb1 knockout phenotypes. About 50% of T gfb1 homozygous mutant (Tgfb1(-/-)) and 25% of Tgfb1 heterozygous (Tgfb1(+/ -)) embryos die during embryogenesis. In a mixed NIH/OIa x C57BL/6J/OIa x 1 29 background partial embryonic lethality of the Tgfb1(-/-) embryos occurs due to defective yolk sac vasculopoiesis and/or hematopoiesis. We show here that on a predominantly CF-1 genetic background, lack of TGF beta 1 causes a pre-morula lethality in about 50% of the null embryos. This partial leth ality is not reversed by transfer of Tgfb1(-/-) embryos to Tgfb1(+/+) hosts . The extent of embryonic lethality in Tgfb1(-/-) embryos ranges in a backg round dependent manner from 20% to 100%. Based on these and other studies i t is clear that TGF beta 1 acts at two distinct phases of embryogenesis: pr e-implantation development and yolk sac vasculogenesis/hematopoiesis. The s usceptibility for the pre-implantation lethality depends on a small number of genetic modifiers since a small number of backcrosses onto the high susc eptibility strain C57BL/6 leads to complete penetrance of the lethality. (C ) 1999 Wiley-Liss, Inc.