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.
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Adeyemo O, Kallio PJ, Palvimo JJ, Kontula K, Janne OA
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.
Hum Mol Genet. 1993 Nov;2(11):1809-12.
- PubMed ID
- 8281140 [ View in PubMed]
- Abstract
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 androgen-response 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.