A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse

W. W. He, M. V. Kumar, D. J. Tindall

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

The testicular feminized (Tfm) mouse lacks completely androgen responsiveness; and therefore, is unique for studying the role of androgenic steroids in different biological processes. In order to understand the molecular basis of this mutation, 2.8 kilobases of cDNA encoding the Tfm mouse androgen receptor (AR) were amplified with a polymerase chain reaction (PCR) technique. No large deletion in the coding region of the Tfm mouse AR was detected. However, sequence analysis revealed a single base deletion in the coding region of the Tfm AR mRNA. This mutation, which is located in the amino-terminus domain of the receptor, is predicted to cause a frame-shift in translation resulting in a premature termination of AR synthesis at amino acid 412. In vitro translation studies of the combinant wild type and Tfm AR's demonstrated that the Tfm AR cDNA failed to produce a full-length receptor. Furthermore, the Tfm AR was demonstrated to lack transcriptional activation capability by cotransfection experiments using the Tfm AR with a reporter plasmid of mouse mammary tumor virus long terminal repeat linked to the chloramphenicol acetyltransferase gene. These studies provide evidence of the molecular defect which causes androgen insensitivity in the Tfm mouse.

Original languageEnglish (US)
Pages (from-to)2373-2378
Number of pages6
JournalNucleic Acids Research
Volume19
Issue number9
StatePublished - 1991

Fingerprint

Frameshift Mutation
Androgen Receptors
Androgens
Genes
Complementary DNA
Mouse mammary tumor virus
Biological Phenomena
Mutation
Chloramphenicol O-Acetyltransferase
Terminal Repeat Sequences
Transcriptional Activation
Sequence Analysis
Plasmids
Steroids
Amino Acids
Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Genetics

Cite this

A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse. / He, W. W.; Kumar, M. V.; Tindall, D. J.

In: Nucleic Acids Research, Vol. 19, No. 9, 1991, p. 2373-2378.

Research output: Contribution to journalArticle

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