title: Fshb-iCre mice are efficient and specific Cre deleters for the gonadotrope lineage.
abstract: Genetic analysis of development and function of the gonadotrope cell lineage within mouse anterior pituitary has been greatly facilitated by at least three currently available Cre strains in which Cre was either knocked into the Gnrhr locus or expressed as a transgene from Cga and Lhb promoters. However, in each case there are some limitations including CRE expression in thyrotropes within pituitary or ectopic expression outside of pituitary, for example in some populations of neurons or gonads. Hence, these Cre strains often pose problems with regard to undesirable deletion of alleles in non-gonadotrope cells, fertility and germline transmission of mutant alleles. Here, we describe generation and characterization of a new Fshb-iCre deleter strain using 4.7 kb of ovine Fshb promoter regulatory sequences driving iCre expression exclusively in the gonadotrope lineage within anterior pituitary. Fshb-iCre mice develop normally, display no ectopic CRE expression in gonads and are fertile. When crossed onto a loxP recombination-mediated red to green color switch reporter mouse genetic background, in vivo CRE recombinase activity is detectable in gonadotropes at more than 95% efficiency and the GFP-tagged gonadotropes readily purified by fluorescence activated cell sorting. We demonstrate the applicability of this Fshb-iCre deleter strain in a mouse model in which Dicer is efficiently and selectively deleted in gonadotropes. We further show that loss of DICER-dependent miRNAs in gonadotropes leads to profound suppression of gonadotropins resulting in male and female infertility. Thus, Fshb-iCre mice serve as a new genetic tool to efficiently manipulate gonadotrope-specific gene expression in vivo.
authors.affiliation: Department of Molecular and Integrative Physiology.
authors.forename: Huizhen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Flow Cytometry Core.
authors.forename: Richard
authors.initials: R
authors.lastname: Hastings
authors.affiliation: Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, 27695, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Miller
authors.affiliation: Department of Molecular and Integrative Physiology; Center for Reproductive Sciences, Institute for Reproductive Health and Regenerative Medicine; Department of Pathology and Laboratory Medicine; Department of Neurosurgery, University of Kansas Medical Center, Kansas City, KS, 66160, USA. Electronic address: tkumar@kumc.edu.
authors.forename: T Rajendra
authors.initials: TR
authors.lastname: Kumar
mesh_terms: D000818:Animals; D002417:Cattle; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005298:Fertility; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics*; D052681:Gonadotrophs / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; C045073:Cre recombinase; D019426:Integrases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Cre; Dicer; Gonadotrope; Ovary; Pituitary; Testis