Utility of progesterone receptor-ires-Cre to generate conditional knockout mice for uterine study

Abstract

In mice, the conditional knockout strategy using the Cre-loxP system is useful for various types of research. The Cre mouse line with progesterone receptor promoter (Pgr^Cre ) has been widely used to produce specific uterine gene-deficient mice, but in the Cre line, endogenous Pgr gene is replaced by Cre recombinase gene, which makes the breeding of homozygous mice (Pgr^Cre/Cre ) difficult because they are infertile. Yang et al. (2013, https://10.1016/j.cell.2013.04.017) reported the generation of another Pgr^iresCre mouse line that still has endogenous Pgr gene, and they inserted Cre recombinase downstream of the Pgr gene via an internal ribosome entry site (IRES). It is possible that this new Pgr^iresCre line would be useful for uterine research as the mice can be bred as homozygotes (Pgr^{iresCre/iresCre} ). Herein, we confirmed the Pgr^iresCre mice effectively directed recombination in the female reproductive tract and was capable of genetic alteration in the endometrium that enables the studies of its uterine function. Our findings demonstrate that the new Pgr^iresCre mouse line is also useful for the generation of uterine-specific knockout mice. The findings using Pgr^iresCre mouse will contribute to the understanding of reproductive systems and diseases in humans and domestic animals.

Keywords: Cre-loxP system; progesterone receptor; uterine function; β-galactosidase (β-gal) staining.