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利用 CRISPR-Cas9 基因组编辑技术生成和分析缺乏 Prss28 和 Prss29 的小鼠。

Generation and analysis of Prss28 and Prss29 deficient mice using CRISPR-Cas9 genome-editing.

机构信息

Division of Animal Sciences, Gynecology, and Women's Health, University of Missouri, Columbia, Missouri, USA.

Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, Missouri, USA.

出版信息

Mol Reprod Dev. 2021 Jul;88(7):482-489. doi: 10.1002/mrd.23473. Epub 2021 May 10.

DOI:10.1002/mrd.23473
PMID:33973295
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8530251/
Abstract

Glands of the uterus are essential for the establishment of pregnancy in mice and their products regulate embryo implantation and stromal cell decidualization critical for pregnancy establishment. Forkhead box A2 (FOXA2) is expressed specifically in the glands and a critical regulator of their differentiation, development and function. Progesterone and FOXA2 regulate members of a serine proteinase gene family (Prss28 and Prss29). Here, CRISPR-Cas9 genome-editing was used to create mice with a heterozygous or homozygous deletion of Prss28 or/and Prss29 to determine their biological roles in uterine function. Female mice lacking Prss28 and Prss29 or both developed normally and were fertile without alterations in uterine histoarchitecture, uterine gland number, or and gene expression. Thus, Prss28 and Prss29 are dispensable for female fertility and do not impact endometrial gland development or uterine function mice.

摘要

子宫腺体对于小鼠妊娠的建立至关重要,其产物调节胚胎着床和基质细胞蜕膜化,这对于妊娠的建立至关重要。叉头框蛋白 A2(FOXA2)特异性表达于腺体中,是其分化、发育和功能的关键调节因子。孕激素和 FOXA2 调节丝氨酸蛋白酶基因家族(Prss28 和 Prss29)的成员。在这里,使用 CRISPR-Cas9 基因组编辑技术创建了杂合或纯合缺失 Prss28 或/和 Prss29 的小鼠,以确定它们在子宫功能中的生物学作用。缺乏 Prss28 和 Prss29 或两者的雌性小鼠正常发育且具有生育能力,子宫组织学结构、子宫腺体数量或基因表达均未发生改变。因此,Prss28 和 Prss29 对于雌性生育能力不是必需的,并且不影响子宫内膜腺体的发育或小鼠的子宫功能。

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本文引用的文献

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Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23952-23959. doi: 10.1073/pnas.2014272117. Epub 2020 Sep 8.
2
Pancreatic secretory trypsin inhibitor reduces multi-organ injury caused by gut ischemia/reperfusion in mice.胰腺分泌性胰蛋白酶抑制剂可减少小鼠肠缺血/再灌注引起的多器官损伤。
PLoS One. 2020 Jan 10;15(1):e0227059. doi: 10.1371/journal.pone.0227059. eCollection 2020.
3
Uterine Glands: Developmental Biology and Functional Roles in Pregnancy.子宫腺体:发育生物学及妊娠中的功能作用。
Endocr Rev. 2019 Oct 1;40(5):1424-1445. doi: 10.1210/er.2018-00281.
4
Integrative analysis of the forkhead box A2 (FOXA2) cistrome for the human endometrium.人子宫内膜中叉头框 A2(FOXA2)顺式作用元件的综合分析。
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5
Uterine glands coordinate on-time embryo implantation and impact endometrial decidualization for pregnancy success.子宫腺体协调胚胎适时着床,并影响子宫内膜蜕膜化以实现妊娠成功。
Nat Commun. 2018 Jun 22;9(1):2435. doi: 10.1038/s41467-018-04848-8.
6
Tridimensional visualization reveals direct communication between the embryo and glands critical for implantation.三维可视化显示胚胎与植入关键腺体之间存在直接沟通。
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