Determination of the physiological and pathological roles of E2F3 in adult tissues

Ivonne Gamper, Deborah L. Burkhart, Megan J. Bywater, Daniel Garcia, Catherine H Wilson, Peter A. Kreuzaler, Mark Arends, Yao-Wu Zheng, Alessandra Perfetto, Trevor D. Littlewood, Gerard I Evan

Research output: Contribution to journalArticlepeer-review

Abstract

Genetically engineered mice have made an enormous contribution towards the elucidation of human disease. However, previously it has not been possible to tune the level of expression of an endogenous gene. Here we describe compound genetically modified mice in which expression of the endogenous E2f3 gene can be either reversibly elevated or repressed by oral administration of tetracycline. This method is, in theory, applicable to any endogenous gene and will allow simple determination of both elevated and reduced expression in physiological and pathological processes. Using this system we demonstrated that elevated levels of E2F3 drive ectopic proliferation in multiple tissues, while repression of E2F3 has minimal impact on tissue proliferation or homeostasis in the majority of contexts. However, in the absence of E2F1 and E2F2, repression of E2F3 resulted in profound reduction of proliferation in the hematopoietic compartments and was rapidly lethal in adult animals.
Original languageEnglish
JournalScientific Reports
Early online date30 Aug 2017
DOIs
Publication statusE-pub ahead of print - 30 Aug 2017

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