In vitro functional characterization of androgen receptor gene mutations at arginine p.856 of the ligand-binding-domain associated with androgen insensitivity syndrome

Asma Tajouri, Maher Kharrat*, Mediha Trabelsi, Ridha M'rad, Olaf Hiort, Ralf Werner

*Korrespondierende/r Autor/-in für diese Arbeit

Abstract

Androgens are critical for male sex differentiation. Their actions are mediated by the androgen receptor (AR). Mutations disrupting AR function result in the androgen insensitivity syndrome (AIS). In this study, we identified in a patient with complete AIS, a novel AR mutation p.R856L. To investigate the functional properties of p.R856L, we performed functional studies. In comparison, we have characterized two already described mutations: p.R856H and p.R856C. We used a model composed of two different promoters fused to a reporter gene, two cell lines, and showed that all mutations were able to transactivate the (ARE)2-TATA promoter expressed in CHO cells more highly. Moreover, we confirmed the pathogenicity of the p.R856L and p.R856C mutations, and their associations with complete AIS. In contrast, the p.R856H mutation, which is associated with a spectrum of AIS phenotypes, showed less severe transcriptional constraints. Altogether, our studies allowed us to better characterize arginine residue at p.R856 position.

OriginalspracheEnglisch
Aufsatznummer105834
ZeitschriftJournal of Steroid Biochemistry and Molecular Biology
Jahrgang208
Seiten (von - bis)105834
ISSN0960-0760
DOIs
PublikationsstatusVeröffentlicht - 04.2021

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  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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