RGD Reference Report - A single base mutation in the androgen receptor gene causes androgen insensitivity in the testicular feminized rat. - Rat Genome Database

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A single base mutation in the androgen receptor gene causes androgen insensitivity in the testicular feminized rat.

Authors: Yarbrough, WG  Quarmby, VE  Simental, JA  Joseph, DR  Sar, M  Lubahn, DB  Olsen, KL  French, FS  Wilson, EM 
Citation: Yarbrough WG, etal., J Biol Chem 1990 May 25;265(15):8893-900.
RGD ID: 1298681
Pubmed: PMID:2341409   (View Abstract at PubMed)

The complete form of androgen insensitivity is an inherited X-linked syndrome in which genetic males fail to undergo masculinization in utero due to defective functioning of the androgen receptor (AR). The molecular basis of androgen insensitivity was investigated in the testicular feminized (Tfm) rat with this syndrome. AR mRNA size and amount, as well as nuclear AR protein revealed by immunocytochemistry, suggested normal expression of the AR gene in the Tfm rat. Sequence analysis of the AR coding region from Tfm and wild-type littermate male rats revealed a single transition mutation, guanine to adenine, within exon E, changing arginine 734 to glutamine within the steroid-binding domain of the AR. This arginine is highly conserved among the family of nuclear receptors and may be part of a phosphorylation recognition site. A recreated mutant AR (Arg734----Gln) expressed in COS cells had only 10-15% of the androgen-binding capacity of wild-type AR; the reduced androgen-binding capacity was similar to that of AR in tissue extracts of the Tfm rat. Stimulation of transcriptional activity by the recreated mutant AR was reduced relative to wild-type AR in cotransfection assays in CV1 cells using as reporter plasmid the mouse mammary tumor virus promoter linked to the chloramphenicol acetyltransferase gene. Thus, arginine 734 appears essential for normal AR function both in androgen binding and transcriptional activation. Absence of these functions results in androgen insensitivity and lack of male sexual development.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KHRatcomplete androgen insensitivity syndrome  IAGP compared to wild typeRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ArRatandrogen receptor signaling pathway  IMP  RGD 
ArRatcellular response to steroid hormone stimulus  IEP methyltrienoloneRGD 
ArRatmale sex differentiation  IMP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ArRatandrogen binding  IMP  RGD 
ArRatnuclear receptor activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ar  (androgen receptor)

Strains
KH  (NA)


Additional Information