A single base mutation in the androgen receptor gene causes androgen insensitivity in the testicular feminized rat.

摘要: The complete form of androgen insensitivity is an inherited X-linked syndrome in which genetic males fail to undergo masculinization utero due defective functioning the receptor (AR). molecular basis was investigated testicular feminized (Tfm) rat with this syndrome. AR mRNA size and amount, as well nuclear protein revealed by immunocytochemistry, suggested normal expression gene Tfm rat. Sequence analysis coding region from wild-type littermate male rats a single transition mutation, guanine adenine, within exon E, changing arginine 734 glutamine steroid-binding domain AR. This highly conserved among family receptors may be part phosphorylation recognition site. A recreated mutant (Arg734----Gln) expressed COS cells had only 10-15% androgen-binding capacity AR; reduced similar that tissue extracts Stimulation transcriptional activity relative cotransfection assays CV1 using reporter plasmid mouse mammary tumor virus promoter linked chloramphenicol acetyltransferase gene. Thus, appears essential for function both binding activation. Absence these functions results lack sexual development.