HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Notini, A J Articles by Zajac, J D Search for Related Content PubMed PubMed Citation Articles by Notini, A J Articles by Zajac, J D

Department of Medicine, University of Melbourne, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia

(Requests for offprints should be addressed to J D Zajac; Email: j.zajac{at}unimelb.edu.au)

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.

This article has been cited by other articles:

				H. E. MacLean, W. S. M. Chiu, A. J. Notini, A.-M. Axell, R. A. Davey, J. F. McManus, C. Ma, D. R. Plant, G. S. Lynch, and J. D. Zajac Impaired skeletal muscle development and function in male, but not female, genomic androgen receptor knockout mice FASEB J, August 1, 2008; 22(8): 2676 - 2689. [Abstract] [Full Text] [PDF]

				U. Simanainen, K. McNamara, R. A. Davey, J. D. Zajac, and D. J. Handelsman Severe Subfertility in Mice with Androgen Receptor Inactivation in Sex Accessory Organs But Not in Testis Endocrinology, July 1, 2008; 149(7): 3330 - 3338. [Abstract] [Full Text] [PDF]

				H. E. MacLean, W. S. M. Chiu, C. Ma, J. F. McManus, R. A. Davey, R. Cameron, A. J. Notini, and J. D. Zajac A floxed allele of the androgen receptor gene causes hyperandrogenization in male mice Physiol Genomics, March 10, 2008; 33(1): 133 - 137. [Abstract] [Full Text] [PDF]

				K.A. Walters, C.M. Allan, and D.J. Handelsman Androgen Actions and the Ovary Biol Reprod, March 1, 2008; 78(3): 380 - 389. [Abstract] [Full Text] [PDF]

				K. A. Walters, C. M. Allan, M. Jimenez, P. R. Lim, R. A. Davey, J. D. Zajac, P. Illingworth, and D. J. Handelsman Female Mice Haploinsufficient for an Inactivated Androgen Receptor (AR) Exhibit Age-Dependent Defects That Resemble the AR Null Phenotype of Dysfunctional Late Follicle Development, Ovulation, and Fertility Endocrinology, August 1, 2007; 148(8): 3674 - 3684. [Abstract] [Full Text] [PDF]

				U. Simanainen, C. M. Allan, P. Lim, S. McPherson, M. Jimenez, J. D. Zajac, R. A. Davey, and D. J. Handelsman Disruption of Prostate Epithelial Androgen Receptor Impedes Prostate Lobe-Specific Growth and Function Endocrinology, May 1, 2007; 148(5): 2264 - 2272. [Abstract] [Full Text] [PDF]

				R P Amann and D N R Veeramachaneni Cryptorchidism in common eutherian mammals Reproduction, March 1, 2007; 133(3): 541 - 561. [Abstract] [Full Text] [PDF]

				A.-M. Axell, H. E. MacLean, D. R. Plant, L. J. Harcourt, J. A. Davis, M. Jimenez, D. J. Handelsman, G. S. Lynch, and J. D. Zajac Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E506 - E516. [Abstract] [Full Text] [PDF]

				R. A. Davey and H. E. MacLean Current and future approaches using genetically modified mice in endocrine research Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E429 - E438. [Abstract] [Full Text] [PDF]