Division of Animal Sciences, University of Missouri, Columbia, Missouri, USA.
Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, Missouri, USA.
Genesis. 2022 Dec;60(10-12):e23493. doi: 10.1002/dvg.23493. Epub 2022 Jul 22.
All mammalian uteri contain glands in their endometrium that develop only or primarily after birth. In mice, those endometrial glands govern post implantation pregnancy establishment via regulation of blastocyst implantation, stromal cell decidualization, and placental development. Here, we describe a new uterine glandular epithelium (GE) specific Cre recombinase mouse line that is useful for the study of uterine gland function during pregnancy. Utilizing CRISPR-Cas9 genome editing, Cre recombinase was inserted into the endogenous serine protease 29 precursor (Prss29) gene. Both Prss29 mRNA and Cre recombinase activity was specific to the GE of the mouse uterus following implantation, but was absent from other areas of the female reproductive tract. Next, Prss29-Cre mice were crossed with floxed forkhead box A2 (Foxa2) mice to conditionally delete Foxa2 specifically in the endometrial glands. Foxa2 was absent in the glands of the post-implantation uterus, and Foxa2 deleted mice exhibited complete infertility after their first pregnancy. These results establish that Prss29-Cre mice are a valuable resource to elucidate and explore the functions of glands in the adult uterus.
所有哺乳动物的子宫在内膜中都含有仅在出生后或主要在出生后发育的腺体。在小鼠中，这些子宫内膜腺体通过调节胚泡着床、基质细胞蜕膜化和胎盘发育来控制着床后妊娠的建立。在这里，我们描述了一种新的子宫腺上皮（GE）特异性 Cre 重组酶小鼠品系，可用于研究妊娠期间子宫腺的功能。利用 CRISPR-Cas9 基因组编辑，将 Cre 重组酶插入内源性丝氨酸蛋白酶 29 前体（Prss29）基因中。在着床后，Prss29-Cre 小鼠的子宫 GE 中均有 Prss29 mRNA 和 Cre 重组酶活性，但在女性生殖道的其他部位不存在。接下来，将 Prss29-Cre 小鼠与 Foxa2 基因敲入小鼠杂交，以在子宫内膜腺中条件性删除 Foxa2。Foxa2 在着床后的子宫腺中缺失，Foxa2 缺失的小鼠在第一次怀孕后完全不育。这些结果表明 Prss29-Cre 小鼠是阐明和探索成年子宫中腺体功能的宝贵资源。
