A shortened tamoxifen induction scheme to induce CreER recombinase without side effects on the male mouse skeleton

Molecular and Cellular Endocrinology
Ferran JardíDirk Vanderschueren

Abstract

The selective estrogen receptor modulator tamoxifen exerts estrogen agonistic or antagonistic actions on several tissues, including bone. The off-target effects of tamoxifen are one of the most widely recognized pitfalls of tamoxifen-inducible Cre recombinases (CreERs), potentially confounding the phenotypic findings. Still, the validation of tamoxifen induction schemes that minimize the side effects of the drug has not been addressed. Here, we compared the side effects on the skeleton and other androgen-responsive targets of a shortened tamoxifen regimen (2 doses of 190 mg/kg body weight by oral gavage) to a standard protocol (4 doses) and determined their efficiency in inducing CreER-mediated gene deletion. In addition, both a vehicle- and a 10-dose group, which served as a positive control for tamoxifen side effects, were also included. For this purpose, we generated male mice with a floxed androgen receptor (AR) and a neuron-specifically expressed CreER. Treatment with two doses of tamoxifen was the only regimen that did not diminish androgenic bioactivity, as assessed by both seminal vesicles and levator ani/bulbocavernosus muscle weights and serum testosterone concentrations. Similarly, trabecular and cortical femoral bon...Continue Reading

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Citations

Mar 14, 2018·The Journal of Endocrinology·Claes OhlssonSofia Movérare-Skrtic
Nov 30, 2018·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Ferran JardíDirk Vanderschueren
Mar 7, 2018·The Aging Male : the Official Journal of the International Society for the Study of the Aging Male·Sok Kuan WongKok-Yong Chin
Jun 8, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Whitney A BullockAlexander G Robling
Apr 3, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Na Ri KimDirk Vanderschueren
Mar 4, 2020·American Journal of Physiology. Endocrinology and Metabolism·Claes OhlssonMarie K Lagerquist
Feb 2, 2019·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Liang ZhaoMin Du
May 11, 2018·The Journal of Endocrinology·Ferran JardíFrank Claessens
Feb 10, 2021·International Journal of Molecular Sciences·Noirrit-Esclassan EmmanuelleVinel Alexia

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