A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicularfeminized mouse
Year: 1991
Type: article
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 recombinant 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.
Source: Nucleic Acids Research
Authors: Wei Wu He, M.Vijay Kumar, Donald J. Tindall
Institutions: Mayo Clinic, Baylor College of Medicine
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1997083861