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 TGFβ1 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 TGFβ1 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 341-349 |
| Number of pages | 9 |
| Journal | Molecular Reproduction and Development |
| Volume | 52 |
| Issue number | 4 |
| DOIs | |
| State | Published - 1999 |
| Externally published | Yes |
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Keywords
- Development
- Gene targeting
- Growth factors
- Knockout mouse
- Lethality
- Pre-implantation
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Genetics
Cite this
Strain dependency of TGFβ1 function during embryogenesis. / Kallapur, Suhas; Ormsby, Ilona; Doetschman, Thomas C.
In: Molecular Reproduction and Development, Vol. 52, No. 4, 1999, p. 341-349.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Strain dependency of TGFβ1 function during embryogenesis
AU - Kallapur, Suhas
AU - Ormsby, Ilona
AU - Doetschman, Thomas C
PY - 1999
Y1 - 1999
N2 - 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 TGFβ1 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 TGFβ1 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.
AB - 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 TGFβ1 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 TGFβ1 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.
KW - Development
KW - Gene targeting
KW - Growth factors
KW - Knockout mouse
KW - Lethality
KW - Pre-implantation
UR - http://www.scopus.com/inward/record.url?scp=0032588796&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032588796&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1098-2795(199904)52:4<341::AID-MRD2>3.0.CO;2-N
DO - 10.1002/(SICI)1098-2795(199904)52:4<341::AID-MRD2>3.0.CO;2-N
M3 - Article
C2 - 10092113
AN - SCOPUS:0032588796
VL - 52
SP - 341
EP - 349
JO - Molecular Reproduction and Development
JF - Molecular Reproduction and Development
SN - 1040-452X
IS - 4
ER -