Kallapur S, Ormsby I, Doetschman T
Division of Neonatology and Pulmonary Biology, Children's Hospital Medical Center, University of Cincinnati, Ohio 45229, USA.
Mol Reprod Dev. 1999 Apr;52(4):341-9. doi: 10.1002/(SICI)1098-2795(199904)52:4<341::AID-MRD2>3.0.CO;2-N.
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.
Tgfβ1基因敲除表型存在不完全显性。约50%的Tgfβ1纯合突变体（Tgfβ1-/-）和25%的Tgfβ1杂合子（Tgfβ1+/-）胚胎在胚胎发育过程中死亡。在NIH/Ola、C57BL/6J/Ola和129混合背景下，Tgfβ1-/-胚胎出现部分胚胎致死率，这是由于卵黄囊血管生成和/或造血功能缺陷所致。我们在此表明，在以CF-1为主的遗传背景下，缺乏TGFβ1会导致约50%的纯合缺失胚胎在桑葚胚前期死亡。这种部分致死率不会因将Tgfβ1-/-胚胎移植到Tgfβ1+/-宿主中而得到逆转。Tgfβ1-/-胚胎的胚胎致死率在不同背景下从20%到100%不等。基于这些研究和其他研究，很明显TGFβ1在胚胎发育的两个不同阶段起作用：着床前发育和卵黄囊血管生成/造血。着床前致死率的易感性取决于少数遗传修饰因子，因为与高易感性品系C57BL/6进行少量回交就会导致致死率完全显性。
