Microarray analysis of Gene expression in limb muscles of three mouse models of Kennedy disease/SBMA

ABSTRACT: Emerging evidence implicates transcriptional dyseregulation within skeletal muscle in the pathogenesis of Kennedy disease/spinal bulbar muscular atrophy (KD/SBMA). We therefore broadly characterized gene expression in skeletal muscle of three independently generated mouse models of this disorder. The mouse models included a polyglutamine expanded (polyQ) AR knock-in model (AR113Q KI), a polyQ AR transgenic model (AR97Q Tg), and a transgenic mouse which overexpresses wild type AR solely in muscle (HSA-AR Tg). We performed microarray analysis of lower hindlimb muscles taken from these three models using high density oligonucleotide arrays. Changes in gene expression relative to wild type controls were evaluated separately in each strain. We validated our results using quantitative RT-PCR. Patterns of gene expression that are common to all lines and unique to each are described. When considered globally, the degree of overlap between the three models is approximately equivalent, and several patterns of gene expression relevant to the disease process were observed. Notably, patterns of gene expression typical of loss of AR function were observed in all three models, as were alterations in genes involved in cell adhesion, energy balance, Huntingtonâ??s disease, muscle atrophy and myogenesis. By comparing patterns of gene expression in three independent models of KD/SBMA, we have been able to identify candidate genes that might mediate the core myogenic features of KD/SBMA. Keywords: Gene expression in transgenic mice and disease state analysis We used microarray (38.5K oligo mouse array, which contain 35,302 of 70mer oligonucleotide probes largely derived from constitutively expressed exons and 3,482 of controls) to analyze gene expression in limb muscles of transgenic mice. Three mouse models of KD/SBMA were used: HSA-AR, AR113Q knock-in and AR97Q. HSA-AR transgenic male mice (n=5) and their WT brothers (n=8, all mice were 110-130 days of age) were used in this experiment. ARQ113-Knock In males (n=3, 3-4 months of age), and transgenic AR97Q males and WT brothers (n= 6 of each) were used in this study. For both HSA-AR and AR113Q samples, the log2 ratio of experimental samples (Cy5) and reference RNA(Cy3) was obtained, and log2 ratios from mutant samples were then subtracted from log2 ratios from WT controls. AR97Q males (Cy5) were simply compared with their WT brothers (Cy3) using a log2 ratio, rather than being first compared with reference RNA.

ORGANISM(S): Mus musculus

SUBMITTER: Kaiguo Mo 

PROVIDER: E-GEOD-10190 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress