EHF is essential for epidermal and colonic epithelial homeostasis, and suppresses Apc-initiated colonic tumorigenesis
- Reehorst, CM; Nightingale, R; Luk, IY; Jenkins, L; Koentgen, F; Williams, DS; Darido, C; Tan, F; Anderton, H; Chopin, M; Schoffer, K; Eissmann, MF; Buchert, M; Mouradov, D; Sieber, OM; Ernst, M; Dhillon, AS; Mariadason, JM;
Publication Year 2021-06-15, Volume 148, Issue #12, Page dev199542
- Journal Title
- 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.
- Adenoma; Colon; Differentiation; Ehf; Epidermis; Epithelium; Ets
- WEHI Research Division(s)
- Inflammation; Immunology; Personalised Oncology
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-06-30 12:00:57Last Modified: 2021-07-20 03:01:25