title: A floxed allele of the androgen receptor gene causes hyperandrogenization in male mice.
abstract: We previously generated a conditional floxed mouse line to study androgen action, in which exon 3 of the androgen receptor (AR) gene is flanked by loxP sites, with the neomycin resistance gene present in intron 3. Deletion of exon 3 in global AR knockout mice causes androgen insensitivity syndrome, characterized by genotypic males lacking normal masculinization. We now report that male mice carrying the floxed allele (AR(lox)) have the reverse phenotype, termed hyperandrogenization. AR(lox) mice have increased mass of androgen-dependent tissues, including kidney, (P < 0.001), seminal vesicle (P < 0.001), levator ani muscle (P = 0.001), and heart (P < 0.05). Serum testosterone is not significantly different. Testis mass is normal, histology shows normal spermatogenesis, and AR(lox) males are fertile. AR(lox) males also have normal AR mRNA levels in kidney, brain, levator ani, liver, and testis. This study reaffirms the need to investigate the potential phenotypic effects of floxed alleles in the absence of cre in tissue-specific knockout studies. In addition, this androgen hypersensitivity model may be useful to further investigate the effects of subtle perturbations of androgen action in a range of androgen-responsive systems in the male.
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia. hmaclean@unimelb.edu.au
authors.forename: Helen E
authors.initials: HE
authors.lastname: MacLean
authors.forename: W S Maria
authors.initials: WS
authors.lastname: Chiu
authors.forename: Cathy
authors.initials: C
authors.lastname: Ma
authors.forename: Julie F
authors.initials: JF
authors.lastname: McManus
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Davey
authors.forename: Rhoda
authors.initials: R
authors.lastname: Cameron
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Notini
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zajac
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006321:Heart / Q000033:anatomy & histology; D017588:Hyperandrogenism / Q000235:genetics*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000033:anatomy & histology; D008099:Liver / Q000033:anatomy & histology; D019656:Loss of Heterozygosity / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D013737:Testis / Q000033:anatomy & histology / Q000166:cytology; D013739:Testosterone / Q000097:blood
chemical_list: D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; C045073:Cre recombinase; D019426:Integrases