Androgen receptor functions from reverse genetic models.

Abstract

The androgen receptor (AR) is a ligand-dependent transcription factor involved in the regulation of many different physiological processes. AR dysfunction causes a diverse range of clinical conditions, including testicular feminization mutation (Tfm) syndrome, prostate cancer, and motor neuron disease (Kennedy's disease). However, due to lack of genetic models, the molecular basis of the AR in these disorders remains largely unknown. Using a conditional targeting technique based on the Cre-loxP system, we successfully generated null AR mutant (ARKO) mice. ARKO males exhibited normal healthy growth, but showed typical Tfm abnormalities. Hormonal assay of ARKO males revealed that while serum androgen levels were very low, estrogen levels were normal. Another hallmark of ARKO males was late-onset obesity, with marked accumulation of white adipose tissue. To clarify the role of human AR (hAR) mutants with expanded polyQ stretches as observed in neurodegenerative disease, we also established a Drosophila model in which either wild-type or polyQ-expanded hAR were ectopically expressed. Although no overt phenotype was detected in adult fly-eye neurons expressing mutant hAR, the ingestion of androgen caused marked neurodegeneration.

• Authors: Takahiro Matsumoto, Ken-ichi Takeyama, Takashi Sato, Shigeaki Kato
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 85 Issue 2-5 Pg. 95-9 (Jun 2003) ISSN: 0960-0760 [Print] England
• PMID: 12943692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Receptors, Androgen
• Transcription Factors

Topics

• Animals
• Female
• Humans
• Male
• Mice
• Mice, Knockout
• Models, Genetic
• Muscular Atrophy, Spinal (genetics)
• Receptors, Androgen (deficiency, genetics, physiology)
• Transcription Factors (genetics, physiology)