Fernandez-Valdivia Rodrigo, Jeong Jaewook, Mukherjee Atish, Soyal Selma M, Li Jie, Ying Yan, Demayo Francesco J, Lydon John P
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Genesis. 2010 Feb;48(2):106-13. doi: 10.1002/dvg.20586.
Considering the regulatory complexities of progesterone receptor (PR) action throughout the female reproductive axis and mammary gland, we generated a mouse model that enables conditional ablation of PR function in a spatiotemporal specific manner. Exon 2 of the murine PR gene was floxed to generate a conditional PR allele (PR(flox)) in mice. Crossing the PR(flox/flox) mouse with the ZP3-cre transgenic demonstrated that the PR(flox) allele recombines to a PR null allele (PR(d)). Mice homozygous for the recombined null PR allele (PR(d/d)) exhibit uterine, ovarian, and mammary gland defects that phenocopy those of our previously described PR knockout (PRKO) model. Therefore, this conditional mouse model for PR ablation represents an invaluable resource with which to further define in a developmental and/or reproductive stage-specific manner the individual and integrative roles of distinct PR populations resident in multiple progesterone-responsive target sites.
考虑到孕酮受体(PR)在整个女性生殖轴和乳腺中的作用具有复杂的调控机制,我们构建了一种小鼠模型,能够以时空特异性的方式有条件地消除PR功能。将小鼠PR基因的外显子2进行floxed处理,以在小鼠中产生条件性PR等位基因(PR(flox))。将PR(flox/flox)小鼠与ZP3-cre转基因小鼠杂交,结果表明PR(flox)等位基因重组为PR无效等位基因(PR(d))。重组无效PR等位基因(PR(d/d))的纯合小鼠表现出子宫、卵巢和乳腺缺陷,这些缺陷与我们之前描述的PR基因敲除(PRKO)模型相似。因此,这种用于PR消融的条件性小鼠模型是一种非常宝贵的资源,可用于以发育和/或生殖阶段特异性的方式进一步明确多个孕酮反应性靶位点中不同PR群体的个体和综合作用。