title: Strain dependency of TGFbeta1 function during embryogenesis.
abstract: There is incomplete penetrance to Tgfb1 knockout phenotypes. About 50% of Tgfb1 homozygous mutant (Tgfb1-/-) and 25% of Tgfb1 heterozygous (Tgfb1+/-) embryos die during embryogenesis. In a mixed NIH/Ola x C57BL/6J/Ola x 129 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 TGFbeta1 causes a pre-morula lethality in about 50% of the null embryos. This partial lethality is not reversed by transfer of Tgfb1-/- embryos to Tgfb1-/+ hosts. The extent of embryonic lethality in Tgfb1-/- embryos ranges in a background dependent manner from 20% to 100%. Based on these and other studies it is clear that TGFbeta1 acts at two distinct phases of embryogenesis: pre-implantation development and yolk sac vasculogenesis/hematopoiesis. The susceptibility for the pre-implantation lethality depends on a small number of genetic modifiers since a small number of backcrosses onto the high susceptibility strain C57BL/6 leads to complete penetrance of the lethality.
authors: Division of Neonatology and Pulmonary Biology, Children's Hospital Medical Center, University of Cincinnati, Ohio 45229, USA. kalls0@chmcc.org
authors: S
authors: S
authors: Kallapur
authors: I
authors: I
authors: Ormsby
authors: T
authors: T
authors: Doetschman
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000502:physiology*; D003433:Crosses, Genetic; D004624:Embryo Transfer; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016513:Mice, SCID; D011247:Pregnancy; D013045:Species Specificity; D016212:Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D016212:Transforming Growth Factor beta