EHF is essential for epidermal and colonic epithelial homeostasis, and suppresses Apc-initiated colonic tumorigenesis
| Autor: | Frank Koentgen, John M. Mariadason, Holly Anderton, Laura J. Jenkins, Rebecca Nightingale, Fiona H Tan, Kael Schoffer, Matthias Ernst, Oliver M. Sieber, Charbel Darido, Amardeep S. Dhillon, Michael Chopin, Camilla M. Reehorst, David S. Williams, Ian Y. Luk, Moritz F. Eissmann, Dmitri Mouradov, Michael Buchert |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Genes APC Biology medicine.disease_cause Mice 03 medical and health sciences 0302 clinical medicine Intestinal mucosa medicine Animals Homeostasis Intestinal Mucosa Molecular Biology 030304 developmental biology Mice Knockout 0303 health sciences Goblet cell ETS transcription factor family ETS Homologous Factor Cellular Reprogramming Epithelium Gut Epithelium Cell Transformation Neoplastic medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Colonic Neoplasms Knockout mouse Cancer research Female Goblet Cells Epidermis Carcinogenesis Transcription Factors Developmental Biology |
| Zdroj: | Development. 148 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.199542 |
| Popis: | Ets homologous factor (EHF) is a member of the epithelial-specific Ets (ESE) family of transcription factors. To investigate its role in development and epithelial homeostasis, we generated a series of novel mouse strains in which the Ets DNA-binding domain of Ehf was deleted in all tissues (Ehf−/−) or specifically in the gut epithelium. Ehf−/− mice were born at the expected Mendelian ratio, but showed reduced body weight gain, and developed a series of pathologies requiring most Ehf−/− mice to reach an ethical endpoint before reaching 1 year of age. These included papillomas in the facial skin, abscesses in the preputial glands (males) or vulvae (females), and corneal ulcers. Ehf−/−mice also displayed increased susceptibility to experimentally induced colitis, which was confirmed in intestinal-specific Ehf knockout mice. Gut-specific Ehf deletion also impaired goblet cell differentiation, induced extensive transcriptional reprogramming in the colonic epithelium and enhanced Apc-initiated adenoma development. The Ets DNA-binding domain of EHF is therefore essential for postnatal homeostasis of the epidermis and colonic epithelium, and its loss promotes colonic tumour development. |
| Databáze: | OpenAIRE |
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