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Defects in embryonic development of EGLN1/PHD2 knockdown transgenic mice are associated with induction of Igfbp in the placenta |
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| Authors: | Terence R.S. Ozolin&scaron ,Diane M. Nadeau,Anne S. Klein,Daniel Morton,William H. Brissette |
| Affiliation: | a Department of Pharmacology and Toxicology, Queen’s University, Kingston, ON Canada K7L 3N6 b Department of Antibacterials, Immunology and Cancer, Pfizer Global Research and Development, Groton, CT 06340, USA c Genetically Modified Mice Center of Emphasis, Pfizer Global Research and Development, Groton, CT 06340, USA d Department of General Pharmacology, Pfizer Global Research and Development, Groton, CT 06340, USA e Department of Pathology, Pfizer Global Research and Development, Groton, CT 06340, USA |
| Abstract: | The HIF (hypoxia inducible factor) hydroxylases EGNL1/PHD2 has been implicated in embryonic development. Here we knocked down EGNL1 in vivo by injecting one-cell murine zygotes with lentivirus-containing RNAi. Progeny with demonstrated EGLN1 inhibition had elevated EPO production and erythropoiesis in vivo. The partial inhibition of EGLN1 in utero is embryonic lethal in some, but not all mice on gestation day 14, and is associated with defects in placental and heart development, similar to those noted in the EGLN1 knockout mouse. Importantly, the in utero inhibition of EGNL1 varied greatly between the embryo proper and the placenta. Using this as a tool we show that the embryopathic effects are associated with knockdown of EGNL1 and the associated induction of Igfbp1 (insulin-like growth factor binding protein-1) mRNA in the placenta, but not the embryo. |
| Keywords: | HIF Hydroxylase Transgenic mice RNAi Embryonic development |
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