Structure of messenger RNA of androgen receptor in mice and molecular characterization in Tfm mutant

: Complementary DNA clones covering the complete coding region of the mouse androgen receptor were assembled by enzymatic amplification (PCR) from testicular RNA and genomic DNA and fully sequenced. The deduced amino acid sequence departs from the rat sequence at 21 positions, 20 of which are in the amino-terminal trans-activation domain. A single 10 kb long messenger RNA containing a 3' noncoding portion longer than 5 kb was detected. The murine cDNA sequence provided the basis to examine the testicular feminization (Tfm) mutation at the molecular level. The androgen receptor messenger RNA level was found reduced about 10-fold in the Tfm mice. The expression of the mutant receptor is affected at a post-transcriptional level. A single base deletion in the hexanucleotide stretch 1107-1112, not far from the 3' end of exon 1, introduces a frame-shift that leads to premature termination of the AR protein. Separately initiated polypeptides containing the DNA-binding and the steroid-binding domains of the androgen receptor are produced in vitro by using strong internal translation initiation sites. These carboxyl-terminal polypeptides have the characteristics of the shortened form of the receptor previously described in the tissues of Tfm mice.