The extraembryonic ectoderm (ExE) is essential for mammalian placental formation and survival of the embryo in utero. We have obtained a mouse model lacking the ExE, by targeted deletion of the transcription factor Elf5. Although Elf5 mutant embryos implant and form an ectoplacental cone, no trophoblast stem (TS) cells can be derived, indicating that the absence of ExE is a result of the lack of TS cell maintenance. Embryos without ExE tissue are able to form the anterior visceral endoderm but fail to undergo gastrulation, demonstrating an essential role for the ExE in embryonic patterning during a defined window of development.
The protein synthesis inhibitor cycloheximide (Chx) suppresses prolactin-induced β-casein gene expression in the mammary epithelial cell line COMMA-D. As the mechanism underlying this effect is unclear, the effects of protein synthesis inhibitors on interactions of transcription factors with the β-casein promoter were examined. Suppression of prolactin-induced β-casein gene expression occurred in both COMMA-D cells and primary mammary cell cultures with as little as 2 h protein synthesis inhibition. This was associated with changes in transcription factors interacting at a response element in the proximal region of the rat β-casein promoter. Inhibition of protein synthesis was associated with NF-κB binding at a site immediately 3′ to the Stat5binding site at position 97-89 of the β-casein promoter, suppression of Stat5 DNA-binding activity, and inhibition of Stat5 tyrosine phosphorylation. Treatment with the NF-κB inhibitor parthenolide failed to restore prolactin responsiveness. These results show that protein synthesis inhibition is associated with both blockage of prolactin-Stat5 signaling and NF-κB binding to the β-casein promoter, but that the latter is not necessary for the suppression of β-casein expression.
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