Aberrant splicing of androgenic receptor mRNA results in synthesis of a nonfunctional receptor protein in a patient with androgen insensitivity
- Erasmus Univ., Rotterdam (Netherlands)
- Univ. of Bonn (Germany)
- Medical Biological Laboratory-Organization for Applied Scientific Research, Rijswijk (Netherlands)
- Glasgow Univ. (United Kingdom)
Androgen insensitivity is a disorder in which the correct androgen response in an androgen target cell is impaired. The clinical symtpoms of this X chromosome-linked syndrome are presumed to be caused by mutations in the androgen receptor gene. The authors report a G {r arrow} 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 {approx}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.
- OSTI ID:
- 5545406
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:20; ISSN PNASA; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANDROGENS
ANDROSTANES
BIOSYNTHESIS
DISEASES
DNA BASE TRANSITIONS
ESTROGENS
GENE AMPLIFICATION
GENE MUTATIONS
HEREDITARY DISEASES
HORMONES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
MEMBRANE PROTEINS
MESSENGER-RNA
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PATIENTS
PROTEINS
RADIORECEPTOR ASSAY
RECEPTORS
RNA
STEROID HORMONES
STEROIDS
SYNTHESIS
TRACER TECHNIQUES
TRANSCRIPTION
TRITIUM COMPOUNDS