Different Cre systems induce differential microRNA landscapes and abnormalities in the female reproductive tracts of Dgcr8 conditional knockout mice. (26th January 2021)

• Record Type: Journal Article
• Authors: Kim, Yeon Sun; Yang, Seung Chel; Park, Mira; Choi, Youngsok; DeMayo, Francesco J.; Lydon, John P.; Kim, Hye‐Ryun; Lim, Hyunjung Jade; Song, Haengseok
• Is Part Of: Cell proliferation. Volume 54:Number 3(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-01-26
• Subjects: Dgcr8 -- Dgcr8 conditional knockout mice -- female reproductive tract -- MicroRNAs -- multiple Cre systems -- Phenotypes; Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.12996
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: Objectives: The female reproductive tract comprises several different cell types. Using three representative Cre systems, we comparatively analysed the phenotypes of Dgcr8 conditional knockout (cKO) mice to understand the function of Dgcr8, involved in canonical microRNA biogenesis, in the female reproductive tract. Materials and Methods: Dgcr8 f/f mice were crossed with Ltf icre/+, Amhr2 cre/+ or PR cre/+ mice to produce mice deficient in Dgcr8 in epithelial ( Dgcr8 ed/ed ), mesenchymal ( Dgcr8 md/md ) and all the compartments ( Dgcr8 td/td ) in the female reproductive tract. Reproductive phenotypes were evaluated in Dgcr8 cKO mice. Uteri and/or oviducts were used for small RNA‐seq, mRNA‐seq, real‐time RT‐PCR, and/or morphologic and histological analyses. Result: Dgcr8 ed/ed mice did not exhibit any distinct defects, whereas Dgcr8 md/md mice showed sub‐fertility and oviductal smooth muscle deformities. Dgcr8 td/td mice were infertile due to anovulation and acute inflammation in the female reproductive tract and suffered from an atrophic uterus with myometrial defects. The microRNAs and mRNAs related to immune modulation and/or smooth muscle growth were systemically altered in the Dgcr8 td/td uterus. Expression profiles of dysregulated microRNAs and mRNAs in the Dgcr8 td/td uterus were different from those in other genotypes in a Cre‐dependent manner. Conclusions: Dgcr8 deficiency with different Cre systems induces overlapping but distinct phenotypes as well as the profiles of microRNAs and their target mRNAs in the female reproductive tract, suggesting the importance of selecting the appropriate Cre driver to investigate the genes of interest. Abstract : We comparatively analysed the phenotypes of Dgcr8 conditional knockout (cKO) mice to understand the function of Dgcr8, involved in canonical microRNA biogenesis, in the female reproductive tract. Because uterine is composed of various cell types, we generated various Dgcr8 cKO mice using representative Cre mice ( Ltf icre/+, Amhr2 cre/+, and PR cre/+ mice) to dissect functions of Dgcr8 depending on uterine cell type‐specific. Each Dgcr8 cKO mice shows distinct and overlapping phenotypes as well as microRNAs and their target mRNA landscapes. These results suggest the importance of selecting the appropriate Cre driver to investigate genes of interest