Significance of the CAG repeat length in the androgen receptor gene (AR) for the transactivation function of an M780I mutant AR

Mutations in the androgen receptor gene (AR) cause a wide spectrum of andro gen insensitivity syndromes (AIS). Mutation analysis of patients with AIS h as revealed that the same missense mutation of the AR gene can give rise to strongly divergent phenotypes suggesting the influence of modifying factor s. The polymorphic CAG repeat in the first exon of the AR gene may be such a modifying factor. The influence of the length of the CAG repeat on the tr ansactivation function of the M780I-mutant AR (causing partial and complete AIS) has been determined by cotransfection of HeLa cells with various CAG- AR expression vectors and a highly androgen-responsive luciferase reporter gene construct. The transcriptional activity of the M780I mutant AR can be, in contrast to the wild-type AR, considerably enhanced by non-physiologica lly high androgen concentrations. Furthermore, an inverse relationship betw een the number of the CAG repeats in the mutant AR and its activity has bee n observed.