Tamoxifen induces cleft palate in mice

Tamoxifen (TAM), a widely-used drug in treating breast cancer, has been reported to be associated with craniofacial defects including micrognathia and cleft palate in humans. However, the exact effects of TAM on the developing palate remain unclear. In the present study, we conclude that excess TAM exposure causes cleft palate defect in mice by regulating MAPK pathways, which implicates the importance of tightly regulated MAPK signaling in palate development and provides a basis for further exploration of the molecular etiology of cleft palate defects caused by environmental factors. Overall design: The anterior and posterior portions of the palatal shelves were dissected out from E13.5 TAM-treated mice and controls (n = 3 for each group), respectively, and subjected to total RNA extraction (RNeasy Micro Kit, cat. 74004; Qiagen). The quality and quantity of RNAs were determined by using a Qubit 2.0 Fluorometric Quantitation system (Life Technologies). Finally, the RNAs were subjected to RNA-Seq analysis. Gene Ontology and pathway categories were grouped according to functional theme and proportion of cases that were affected by individual pathway alterations was plotted per subgroup, and across series.