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Title: Genomic actions of the androgen receptor are required for normal male sexual differentiation in a mouse model.
Austin Authors: Notini, Amanda J;Davey, Rachel A;McManus, J F;Bate, K L;Zajac, J D
Affiliation: Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 1-Dec-2005
Publication information: Journal of Molecular Endocrinology; 35(3): 547-55
Abstract: Androgens mediate their effects in target cells via the androgen receptor (AR), which acts predominantly as a ligand-dependent transcription factor. In addition, androgens induce rapid activation of second messenger signal transduction cascades, and this is thought to occur via non-genomic mechanisms. We have used the Cre/loxP system to generate an AR knockout (ARKO) mouse targeting exon 3, which encodes the second zinc finger of the DNA-binding domain. To generate universal ARKO mice, floxed AR mice were mated with CMV-Cre mice, which express Cre recombinase ubiquitously. Deletion of the floxed allele in our mice does not disrupt the reading frame, and has been designed so that the mutant AR can bind ligand but not target genes. ARKO males displayed a complete androgen insensitivity phenotype, with female external genitalia and a reduction in body weight compared with wild-type males (P < 0.001). Testes of ARKO males were smaller than control males (P < 0.0001) and were located intra-abdominally. We have demonstrated that genotypically XY mice lacking the second zinc finger of the AR have a female phenotype, and we conclude that the genomic actions of the AR (mediated by DNA binding) are indispensable for normal male sexual differentiation.
Gov't Doc #: 16326839
DOI: 10.1677/jme.1.01884
Journal: Journal of molecular endocrinology
Type: Journal Article
Subjects: Androgen-Insensitivity Syndrome.genetics.metabolism.pathology
Base Sequence
Binding Sites.genetics
DNA, Complementary.genetics
Gene Targeting
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Receptors, Androgen.chemistry.deficiency.genetics.metabolism
Sex Differentiation.genetics
Zinc Fingers.genetics
Appears in Collections:Journal articles

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