Fshb-iCre mice are efficient and specific Cre deleters for the gonadotrope lineage
Open accessAbstract
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.
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Although multiple mouse models have been used to recapitulate idiopathic hypogonadal hypogonadism (IHH), none have focused on loss of function in cells expressing GnRHR and how ERK signaling may be functioning in these tissue compartments.
“Although multiple mouse models have been used to recapitulate idiopathic hypogonadal hypogonadism (IHH), none have focused on loss of function in cells expressing GnRHR and how ERK signaling may be functioning in these tissue compartments3,64,65.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [65]
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Sex- and Age-Specific Impact of ERK Loss Within the Pituitary Gonadotrope in Mice
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Brown, J. L., Sones, J. L., Angulo, C. N., Abbott, K., Miller, A. D., Boehm, U., & Roberson, M. S. (2019) · Scientific Reports · doi:10.1038/s41598-019-45997-0 · Cited by 13 · see citing works
- Authors
- Wang, H., Hastings, R., Miller, W. L., & Kumar, T. R.
- Affiliations
- North Carolina State University (US)
- University of Kansas Medical Center (US)
- Corresponding author
- Kumar, T. Rajendra
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 419
- Pages
- 124-138
- ISSN
- 0303-7207 (ISSN-L)
- PMC
- PMC4684453
- OpenAlex
- W2178560036
- Cited by
- 19
- References
- 55
- Citations by year
- 2024: 2 · 2023: 2 · 2021: 1 · 2019: 4 · 2018: 5 · 2016: 5
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (AG029531, HD069751, GM104936, CA166557)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- anterior pituitary, gonadotrophs, iCre, microRNA loss, gonadotropin suppression, infertility, fertility, germline transmission
- MeSH terms
- Animals, Cattle, Female, Fertility, Male, Mice, Transgenic, Promoter Regions, Genetic, Integrases, Follicle Stimulating Hormone, beta Subunit, Ribonuclease III, Mice, Gonadotrophs, DEAD-box RNA Helicases
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