© 1993 Oxford University Press
RESEARCH-ARTICLE |
A single-base substitution in exon 6 of the androgen receptor gene causing complete androgen insensitivity: the mutated receptor fails to transactivate but binds to DNA in vitro
1The Population Council and The Rockefeller University New York, NY 10021, USA 2Department of Physiology, University of Helsinki 3Second Department of Medicine, University of Helsinki Helsinki, Finland
*To whom correspondence should be addressed at: Department of Physiology, PO Box 9 (Siltavuorenpenger 20 J), SF-00014 University of Helsinki, Finland
Received July 29, 1993; Revised September 7, 1993; Accepted September 7, 1993
A single-base substitution in the coding region of the androgen receptor (AR) gene caused complete androgen insensitivity in a patient with 46,XY karyotype. The mutation was a T-to-G transition in exon 6 and changed the codon 807 from ATG (methionine) to AGG (arginine) in the hormone-binding domain of the protein. The mutation was inserted into the wild-type human AR cDNA and the resulting cDNA expressed in CV-1 cells. Native and mutated AR proteins synthesized in recipient cells had identical molecular masses. Ligand-binding activity of the mutant receptor was less than 5% of that of the wild-type AR. The mutant's interaction with an androgenresponse element in vitro was identical to that of the native aporeceptor; however, it did not transactivate a reporter gene construct in transfected CV-1 cells. Androgen insensitivity in our patient was thus due to altered structure of the receptor's steroid-binding region, which prevented the mutated AR from gaining a transcriptionally active form in vivo.
+Present address: Tuskegee University, School of Veterinary Medicine, Tuskegee, AL 36088, USA
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