RRC ID 2387
Author Katsuno M, Adachi H, Inukai A, Sobue G.
Title Transgenic mouse models of spinal and bulbar muscular atrophy (SBMA).
Journal Cytogenet Genome Res
Abstract Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by proximal muscle atrophy, weakness, contraction fasciculations, and bulbar involvement. Only males develop symptoms, while female carriers usually are asymptomatic. A specific treatment for SBMA has not been established. The molecular basis of SBMA is the expansion of a trinucleotide CAG repeat, which encodes the polyglutamine (polyQ) tract, in the first exon of the androgen receptor (AR) gene. The pathologic hallmark is nuclear inclusions (NIs) containing the mutant and truncated AR with expanded polyQ in the residual motor neurons in the brainstem and spinal cord as well as in some other visceral organs. Several transgenic (Tg) mouse models have been created for studying the pathogenesis of SBMA. The Tg mouse model carrying pure 239 CAGs under human AR promoter and another model carrying truncated AR with expanded CAGs show motor impairment and nuclear NIs in spinal motor neurons. Interestingly, Tg mice carrying full-length human AR with expanded polyQ demonstrate progressive motor impairment and neurogenic pathology as well as sexual difference of phenotypes. These models recapitulate the phenotypic expression observed in SBMA. The ligand-dependent nuclear localization of the mutant AR is found to be involved in the disease mechanism, and hormonal therapy is suggested to be a therapeutic approach applicable to SBMA.
Volume 100(1-4)
Pages 243-51
Published 2003-1-1
DOI 10.1159/000072860
PII 72860
PMID 14526186
MeSH Animals Disease Models, Animal* Female Humans Male Mice Mice, Transgenic Muscular Atrophy, Spinal / genetics* Muscular Atrophy, Spinal / pathology Phenotype Receptors, Androgen / genetics* Sex Factors Trinucleotide Repeat Expansion / genetics*
IF 1.114
Times Cited 15
Mice RBRC00344 RBRC00373