The androgen receptor in the testicular feminized (Tfm) mouse may be a product of internal translation initiation.
Androgen insensitivity in the testicular feminized (Tfm) mouse is caused by frame-shift mutation in the androgen receptor (AR) mRNA, which results in a stop codon in the amino terminus. Despite this mutation, a smaller sized protein corresponding to the DNA- and steroid-binding domain of the AR can be synthesized from the cloned Tfm AR cDNA by in vitro translation. The Tfm AR construct was demonstrated to express a protein capable of binding androgen with an affinity similar to the cloned wild-type AR. Although the Tfm AR product failed to transactivate mouse mammary tumor virus-long terminal repeat (MMTV-LTR) promoter when low concentrations (100 ng) of Tfm AR vector were cotransfected, higher concentrations (5000 ng) resulted in a residual amount of transactivation, suggesting lower level transactivating capabilities. By cotransfecting the Tfm AR expression vector with the wild-type receptor, it was demonstrated that the product of the Tfm AR gene is capable of inhibiting the transactivation activity of the wild-type receptor. These data suggest that although the Tfm AR mRNA fails to produce a full-length AR because of the frame-shift mutation, a smaller protein capable of binding both steroid and DNA can be produced by translation from an internal initiation codon. This product could account for the low levels of androgen-binding activity detected previously in the Tfm mouse.
He
W W
WW
Department of Urology, Mayo Foundation, Rochester, MN 55905.
Lindzey
J K
JK
Prescott
J L
JL
Kumar
M V
MV
Tindall
D J
DJ
D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D016368:Frameshift Mutation; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics*; D013577:Syndrome; D015533:Transcriptional Activation
D000728:Androgens; D011944:Receptors, Androgen