Tamoxifen administration induces histopathologic changes within the lungs of Cre-recombinase-negative mice: A case report.

Tamoxifen administration induces histopathologic changes within the lungs of Cre-recombinase-negative mice: A case report.
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DOI:
10.1177/00236772211042968
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发表时间:
2022-06
期刊:
影响因子:
2.4
通讯作者:
--
中科院分区:
医学4区
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--
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他莫昔芬通常用作人类癌症治疗,并在研究环境中使用cre-lox小鼠模型诱导遗传改变。然而,他莫昔芬脱靶效应在动物研究中的程度被低估了。在这里,我们报告了三苯氧胺腹腔注射治疗的cre重组酶阴性小鼠细胞浸润的显著变化。在肺部观察到这些变化,其特征为存在肺泡炎、血管炎和胸膜炎。尽管对他莫昔芬治疗有显著的免疫学变化,但未观察到临床症状。这项研究提供了一个警示,他莫昔芬治疗单独导致组织学改变,可能会模糊研究的解释,并进一步强调需要开发替代小鼠模型诱导cre介导的删除。
Tamoxifen is commonly used as a cancer treatment in humans and for inducing genetic alterations using cre-lox mouse models in the research setting. However, the extent of tamoxifen off-target effects in animal research is underappreciated. Here, we report significant changes in cellular infiltration in cre-recombinase-negative mice treated with tamoxifen intraperitoneally. These changes were noted in the lungs, which were characterized by the presence of alveolitis, vasculitis, and pleuritis. Despite significant immunological changes in response to tamoxifen-treatment, clinical symptoms were not observed. This study provides a cautionary note that tamoxifen treatment alone leads to histologic alterations that may obscure research interpretations and further highlights the need for the development of alternative mouse models for inducible cre-mediated deletion.
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