| First Author | Quiroz E | Year | 2025 |
| Journal | Biol Reprod | Volume | 113 |
| Issue | 1 | Pages | 83-96 |
| PubMed ID | 40407141 | Mgi Jnum | J:368606 |
| Mgi Id | MGI:8216815 | Doi | 10.1093/biolre/ioaf090 |
| Citation | Quiroz E, et al. (2025) A Mouse Model Engineered to Spatiotemporally Control Cre Expression in Progesterone Receptor Positive Cells. Biol Reprod |
| abstractText | The Cre/loxP system is widely used for site-specific genetic manipulation in mice. The PgrCremouse model, where Cre recombinase is driven by the progesterone receptor promoter, is commonly used for gene ablation in Pgr-positive uterine cells. However, the PgrCreis active in the neonatal uterus and does not allow temporal control. To enhance the functionality of the PgrCremouse, we generated and characterized an inducible PgriCreERT2mouse, in which iCreERT2is inserted downstream of the endogenous Pgrpromoter. PgriCreERT2mice crossed with Rosa26-CAG-LSL-Sun1-sfGFP-mycreporter mice demonstrated tamoxifen-dependent recombination in uterine stromal fibroblasts and a subset of epithelial cells. Tamoxifen-induced ablation of PGR expression was accomplished by crossing PgriCreERT2mice with the Pgrflox/floxmice. Resulting PgriCreERT2/Pgr:floxand Pgrflox/floxmice were treated with tamoxifen or oil vehicle daily for 3 days and assayed for fertility one month after treatment. Tamoxifen-treated PgriCreERT2/Pgr:floxmice exhibited implantation failure, dysregulation of uterine epithelial and stromal cell proliferation, and loss of decidualization response with no impact on ovulation or embryo transport. A six month breading trial demonstrated that 4/6 tamoxifen-treated PgriCreERT2/Pgr:floxmice were completely infertile, and the remaining 2/6 delivered only 3 total pups each near the end of the trial. In contrast, tamoxifen-treated Cre-negative females were fertile with normal uterine receptivity compared to vehicle controls, indicating that tamoxifen administration with a month-long recovery period did not impair pregnancy. Together, these data demonstrate the utility of this inducible PgriCreERT2mouse model for spatiotemporally controlled gene ablation in Pgr-positive cells of the uterus. |
