title: Transcriptional profile of muscle following acute induction of symptoms in a mouse model of Kennedy's disease/spinobulbar muscular atrophy.
abstract: BACKGROUND
  Kennedy's disease/Spinobulbar muscular atrophy (KD/SBMA) is a degenerative neuromuscular disease affecting males. This disease is caused by polyglutamine expansion mutations of the androgen receptor (AR) gene. Although KD/SBMA has been traditionally considered a motor neuron disease, emerging evidence points to a central etiological role of muscle. We previously reported a microarray study of genes differentially expressed in muscle of three genetically unique mouse models of KD/SBMA but were unable to detect those which are androgen-dependent or are associated with onset of symptoms.
  
  
  RESULTS
  In the current study we examined the time course and androgen-dependence of transcriptional changes in the HSA-AR transgenic (Tg) mouse model, in which females have a severe phenotype after acute testosterone treatment. Using microarray analysis we identified differentially expressed genes at the onset and peak of muscle weakness in testosterone-treated Tg females. We found both transient and persistent groups of differentially expressed genes and analysis of gene function indicated functional groups such as mitochondrion, ion and nucleotide binding, muscle development, and sarcomere maintenance.
  
  
  CONCLUSIONS
  By comparing the current results with those from the three previously reported models we were able to identify KD/SBMA candidate genes that are androgen dependent, and occur early in the disease process, properties which are promising for targeted therapeutics.
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
authors.forename: Katherine
authors.initials: K
authors.lastname: Halievski
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
authors.forename: Kaiguo
authors.initials: K
authors.lastname: Mo
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Westwood
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Monks
mesh_terms: D000818:Animals; D055534:Bulbo-Spinal Atrophy, X-Linked / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D059467:Transcriptome