title: Targeting of GFP-Cre to the mouse Cyp11a1 locus both drives cre recombinase expression in steroidogenic cells and permits generation of Cyp11a1 knock out mice.
abstract: To permit conditional gene targeting of floxed alleles in steroidogenic cell-types we have generated a transgenic mouse line that expresses Cre Recombinase under the regulation of the endogenous Cytochrome P450 side chain cleavage enzyme (Cyp11a1) promoter. Mice Carrying the Cyp11a1-GC (GFP-Cre) allele express Cre Recombinase in fetal adrenal and testis, and adrenal cortex, testicular Leydig cells (and a small proportion of Sertoli cells), theca cells of the ovary, and the hindbrain in postnatal life. Circulating testosterone concentration is unchanged in Cyp11(+/GC) males, suggesting steroidogenesis is unaffected by loss of one allele of Cyp11a1, mice are grossly normal, and Cre Recombinase functions to recombine floxed alleles of both a YFP reporter gene and the Androgen Receptor (AR) in steroidogenic cells of the testis, ovary, adrenal and hindbrain. Additionally, when bred to homozygosity (Cyp11a1(GC/GC) ), knock-in of GFP-Cre to the endogenous Cyp11a1 locus results in a novel mouse model lacking endogenous Cyp11a1 (P450-SCC) function. This unique dual-purpose model has utility both for those wishing to conditionally target genes within steroidogenic cell types and for studies requiring mice lacking endogenous steroid hormone production.
authors.affiliation: Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: O'Hara
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: York
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Pumin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Smith
mesh_terms: D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D018390:Gene Targeting; D049452:Green Fluorescent Proteins / Q000235:genetics*; D019426:Integrases / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D013737:Testis / Q000166:cytology / Q000378:metabolism*
chemical_list: D049452:Green Fluorescent Proteins; D002786:Cholesterol Side-Chain Cleavage Enzyme; C045073:Cre recombinase; D019426:Integrases