RRC ID 2385
Author Katsuno M, Adachi H, Kume A, Li M, Nakagomi Y, Niwa H, Sang C, Kobayashi Y, Doyu M, Sobue G.
Title Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy.
Journal Neuron
Abstract Spinal and bulbar muscular atrophy (SBMA) is a polyglutamine disease caused by the expansion of a CAG repeat in the androgen receptor (AR) gene. We generated a transgenic mouse model carrying a full-length AR containing 97 CAGs. Three of the five lines showed progressive muscular atrophy and weakness as well as diffuse nuclear staining and nuclear inclusions consisting of the mutant AR. These phenotypes were markedly pronounced in male transgenic mice, and dramatically rescued by castration. Female transgenic mice showed only a few manifestations that markedly deteriorated with testosterone administration. Nuclear translocation of the mutant AR by testosterone contributed to the phenotypic difference with gender and the effects of hormonal interventions. These results suggest the therapeutic potential of hormonal intervention for SBMA.
Volume 35(5)
Pages 843-54
Published 2002-8-29
DOI 10.1016/s0896-6273(02)00834-6
PII S0896627302008346
PMID 12372280
MeSH Animals Castration / statistics & numerical data Chickens Disease Models, Animal* Female Gene Expression / physiology* Humans Male Mice Mice, Inbred C57BL Mice, Transgenic Muscular Atrophy, Spinal / genetics* Muscular Atrophy, Spinal / metabolism* Muscular Atrophy, Spinal / pathology Phenotype Receptors, Androgen / biosynthesis Receptors, Androgen / genetics Sex Characteristics Spinal Cord / drug effects Spinal Cord / metabolism Spinal Cord / pathology Testosterone / biosynthesis Testosterone / deficiency* Testosterone / genetics* Testosterone / physiology
IF 14.415
Times Cited 321
Mice RBRC00344 RBRC00373