دورية أكاديمية

Developmental malformations resulting from high-dose maternal tamoxifen exposure in the mouse

التفاصيل البيبلوغرافية
العنوان: Developmental malformations resulting from high-dose maternal tamoxifen exposure in the mouse
المؤلفون: Sun, Miranda R., Steward, Austin C., Sweet, Emma A., Martin, Alexander A., Lipinski, Robert J.
المساهمون: Ruhrberg, Christiana, The University of Wisconsin Office of Vice Chancellor for Graduate and Research Education, National Institutes of Health
المصدر: PLOS ONE ; volume 16, issue 8, page e0256299 ; ISSN 1932-6203
بيانات النشر: Public Library of Science (PLoS)
سنة النشر: 2021
المجموعة: PLOS Publications (via CrossRef)
الوصف: Tamoxifen is an estrogen receptor (ER) ligand with widespread use in clinical and basic research settings. Beyond its application in treating ER-positive cancer, tamoxifen has been co-opted into a powerful approach for temporal-specific genetic alteration. The use of tamoxifen-inducible Cre-recombinase mouse models to examine genetic, molecular, and cellular mechanisms of development and disease is now prevalent in biomedical research. Understanding off-target effects of tamoxifen will inform its use in both clinical and basic research applications. Here, we show that prenatal tamoxifen exposure can cause structural birth defects in the mouse. Administration of a single 200 mg/kg tamoxifen dose to pregnant wildtype C57BL/6J mice at gestational day 9.75 caused cleft palate and limb malformations in the fetuses, including posterior digit duplication, reduction, or fusion. These malformations were highly penetrant and consistent across independent chemical manufacturers. As opposed to 200 mg/kg, a single dose of 50 mg/kg tamoxifen at the same developmental stage did not result in overt structural malformations. Demonstrating that prenatal tamoxifen exposure at a specific time point causes dose-dependent developmental abnormalities, these findings argue for more considerate application of tamoxifen in Cre-inducible systems and further investigation of tamoxifen’s mechanisms of action.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1371/journal.pone.0256299
الإتاحة: https://doi.org/10.1371/journal.pone.0256299Test
حقوق: http://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.49C1B100
قاعدة البيانات: BASE