Rashbrook Victoria S, Denti Laura, Ruhrberg Christiana
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Anim Welf. 2023 Dec 12;32:e78. doi: 10.1017/awf.2023.98. eCollection 2023.
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 (). 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.
他莫昔芬诱导的CreER-LoxP重组常用于在转基因小鼠中诱导时空可控的基因缺失。先前的研究表明，他莫昔芬和他莫昔芬诱导的CreER激活可能会产生应加以控制的脱靶效应。然而，尚未有报道称，在实验室小鼠中，与CreER表达无关的他莫昔芬给药是否会与常用麻醉药物如美托咪定或其对映体右美托咪定产生不良相互作用（）。在此，我们报告，在C57Bl6/J6和129/SvEv混合背景的雄性小鼠中，在他莫昔芬治疗后采用氯胺酮-美托咪定麻醉时，出现尿栓形成和发病的发生率很高。因此，美托咪定在他莫昔芬治疗后的雄性小鼠中为禁忌。由于即使在没有他莫昔芬治疗的情况下，右美托咪定在雄性小鼠中导致发病和死亡的发生率也高于美托咪定，我们的研究结果表明，右美托咪定不是他莫昔芬治疗后雄性小鼠麻醉的合适替代药物。我们得出结论，在使用经过他莫昔芬治疗以诱导CreER-LoxP重组的雄性小鼠的研究中，需要仔细评估麻醉药物的选择。
