# Tamoxifen exacerbates morbidity and mortality in male mice receiving medetomidine anaesthesia

## TL;DR

Tamoxifen treatment in male mice increases health risks when combined with medetomidine or dexmedetomidine anesthesia.

## Contribution

Identifies adverse interactions between tamoxifen and medetomidine/dexmedetomidine in male mice.

## Key findings

- Tamoxifen treatment followed by medetomidine causes high urinary plug formation and morbidity in male mice.
- Dexmedetomidine causes higher mortality in male mice after tamoxifen treatment compared to medetomidine.
- Medetomidine and dexmedetomidine are unsuitable for male mice post-tamoxifen treatment.

## Abstract

Tamoxifen-induced CreER-LoxP recombination is often used to induce spatiotemporally controlled gene deletion in genetically modified mice. Prior work has shown that tamoxifen and tamoxifen-induced CreER activation can have off-target effects that should be controlled. However, it has not yet been reported whether tamoxifen administration, independently of CreER expression, interacts adversely with commonly used anaesthetic drugs such as medetomidine or its enantiomer dexmedetomidine in laboratory mice (Mus musculus). Here, we report a high incidence of urinary plug formation and morbidity in male mice on a mixed C57Bl6/J6 and 129/SvEv background when tamoxifen treatment was followed by ketamine-medetomidine anaesthesia. Medetomidine is therefore contra-indicated for male mice after tamoxifen treatment. As dexmedetomidine causes morbidity and mortality in male mice at higher rates than medetomidine even without tamoxifen treatment, our findings suggest that dexmedetomidine is not a suitable alternative for anaesthesia of male mice after tamoxifen treatment. We conclude that the choice of anaesthetic drug needs to be carefully evaluated in studies using male mice that have undergone tamoxifen treatment for inducing CreER-LoxP recombination.