The androgen receptor in the testicular feminized (Tfm) mouse may be a product of internal translation initiation.

W. W. He, J. K. Lindzey, J. L. Prescott, M. V. Kumar, D. J. Tindall

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)121-134
Number of pages14
JournalReceptor
Volume4
Issue number2
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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    He, W. W., Lindzey, J. K., Prescott, J. L., Kumar, M. V., & Tindall, D. J. (1994). The androgen receptor in the testicular feminized (Tfm) mouse may be a product of internal translation initiation. Receptor, 4(2), 121-134.