Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Mol Endocrinol. 2005 Dec;35(3):547-55.

Genomic actions of the androgen receptor are required for normal male sexual differentiation in a mouse model.

Author information

  • 1Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.

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.

PMID:
16326839
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk