Details

Autor(en) / Beteiligte

• Ris-Stalpers, C.
• G. G. J. M. Kuiper
• Faber, P. W.
• Schweikert, H. U.
• van Rooij, H. C. J.
• Zegers, N. D.
• Hodgins, M. B.
• Degenhart, H. J.
• Trapman, J.
• Brinkmann, A. O.

Titel

Aberrant Splicing of Androgen Receptor mRNA Results in Synthesis of a Nonfunctional Receptor Protein in a Patient with Androgen Insensitivity

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1990-10, Vol.87 (20), p.7866-7870

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1990

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Androgen insensitivity is a disorder in which the correct androgen response in an androgen target cell is impaired. The clinical symptoms of this X chromosome-linked syndrome are presumed to be caused by mutations in the androgen receptor gene. We report a G→ T mutation in the splice donor site of intron 4 of the androgen receptor gene of a 46,XY subject lacking detectable androgen binding to the receptor and with the complete form of androgen insensitivity. This point mutation completely abolishes normal RNA splicing at the exon 4/intron 4 boundary and results in the activation of a cryptic splice donor site in exon 4, which leads to the deletion of 123 nucleotides from the mRNA. Translation of the mutant mRNA results in an androgen receptor protein ≈ 5 kDa smaller than the wild type. This mutated androgen receptor protein was unable to bind androgens and unable to activate transcription of an androgen-regulated reporter gene construct. This mutation in the human androgen receptor gene demonstrates the importance of an intact steroid-binding domain for proper androgen receptor functioning in vivo.