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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., Competing Interests: The authors have declared that no competing interests exist.

The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45-68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate.