| First Author | Flentjar N | Year | 2007 |
| Journal | Gastroenterology | Volume | 132 |
| Issue | 4 | Pages | 1410-9 |
| PubMed ID | 17408644 | Mgi Jnum | J:128593 |
| Mgi Id | MGI:3767525 | Doi | 10.1053/j.gastro.2007.02.054 |
| Citation | Flentjar N, et al. (2007) TGF-betaRII rescues development of small intestinal epithelial cells in Elf3-deficient mice. Gastroenterology 132(4):1410-9 |
| abstractText | BACKGROUND & AIMS: ELF3, a member of the ETS transcription factor family, has been shown to transactivate the transforming growth factor beta type II receptor (TGF-betaRII) promoter. Previously we showed that Elf3-null mice have a defect in the small intestine caused by a failure of small intestinal epithelial cells to differentiate and that these cells produced significantly lower levels of Tgf-betaRII. To prove that the defect observed in Elf3-null mice resulted from the lack of Elf3-dependent activation of Tgf-betaRII expression, we performed a genetic rescue. METHODS: We generated transgenic mice that express human TGF-betaRII specifically in the intestinal epithelium under the control of the mouse A33 antigen promoter. Mice expressing the A33-TGF-betaRII transgene were mated with Elf3(+/-) mice, and double heterozygous offspring harboring both the transgene and one mutant Elf3 allele were intercrossed. RESULTS: The resultant A33-TGF-betaRII transgenic Elf3(-/-) pups displayed normal small intestinal morphology, while the characteristic abnormality was retained in all Elf3(-/-) mice that did not express the transgene. This phenotypic rescue shows for the first time in vivo that a single gene, Elf3, is the critical upstream regulator of Tgf-betaRII in mouse small intestinal epithelium. CONCLUSIONS: This has important implications for our understanding of tissue-specific gene regulation and further strengthens the potential clinical connection between ELF3 and colorectal cancer involving transforming growth factor beta insensitivity. |
