Microarray Analysis of Gene Expression by Skeletal Muscle of Three Mouse Models of Kennedy Disease/Spinal Bulbar Muscular Atrophy
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{"title"=>"Microarray analysis of gene expression by skeletal muscle of three mouse models of Kennedy disease/spinal bulbar muscular atrophy", "type"=>"journal", "authors"=>[{"first_name"=>"Kaiguo", "last_name"=>"Mo", "scopus_author_id"=>"7006378056"}, {"first_name"=>"Zak", "last_name"=>"Razak", "scopus_author_id"=>"36239262300"}, {"first_name"=>"Pengcheng", "last_name"=>"Rao", "scopus_author_id"=>"23028868600"}, {"first_name"=>"Zhigang", "last_name"=>"Yu", "scopus_author_id"=>"55730395300"}, {"first_name"=>"Hiroaki", "last_name"=>"Adachi", "scopus_author_id"=>"35486813000"}, {"first_name"=>"Masahisa", "last_name"=>"Katsuno", "scopus_author_id"=>"7005396497"}, {"first_name"=>"Gen", "last_name"=>"Sobue", "scopus_author_id"=>"55221437100"}, {"first_name"=>"Andrew P.", "last_name"=>"Lieberman", "scopus_author_id"=>"7202118629"}, {"first_name"=>"J.", "last_name"=>"Timothy Westwood", "scopus_author_id"=>"7004670277"}, {"first_name"=>"D.", "last_name"=>"Ashley Monks", "scopus_author_id"=>"6701776195"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"77958530066", "doi"=>"10.1371/journal.pone.0012922", "pui"=>"359839151", "pmid"=>"20886071", "scopus"=>"2-s2.0-77958530066", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"4e2069af-9efb-3441-9c33-2db972cfe7d8", "abstract"=>"BACKGROUND: Emerging evidence implicates altered gene expression 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 disease. The mouse models included a polyglutamine expanded (polyQ) AR knock-in model (AR113Q), a polyQ AR transgenic model (AR97Q), and a transgenic mouse that overexpresses wild type AR solely in skeletal muscle (HSA-AR). HSA-AR mice were included because they substantially reproduce the KD/SBMA phenotype despite the absence of polyQ AR.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: We performed microarray analysis of lower hindlimb muscles taken from these three models relative to wild type controls using high density oligonucleotide arrays. All microarray comparisons were made with at least 3 animals in each condition, and only those genes having at least 2-fold difference and whose coefficient of variance was less than 100% were considered to be differentially expressed. When considered globally, there was a similar overlap in gene changes between the 3 models: 19% between HSA-AR and AR97Q, 21% between AR97Q and AR113Q, and 17% between HSA-AR and AR113Q, with 8% shared by all models. 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, muscle atrophy and myogenesis. We additionally measured changes similar to those observed in skeletal muscle of a mouse model of Huntington's Disease, and to those common to muscle atrophy from diverse causes.\\n\\nCONCLUSIONS/SIGNIFICANCE: 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.", "link"=>"http://www.mendeley.com/research/microarray-analysis-gene-expression-skeletal-muscle-three-mouse-models-kennedy-diseasespinal-bulbar-2", "reader_count"=>40, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>8, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>6, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>8, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>6, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>5, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>10, "Neuroscience"=>5, "Arts and Humanities"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Neuroscience"=>{"Neuroscience"=>5}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Italy"=>1, "Spain"=>1}, "group_count"=>1}

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/828334"], "description"=>"<p>Cluster output represents colorimetrically indicated log2 ratio change. Mutant strains are represented by columns and rows represent a single gene. Clusters of co-regulated genes are labeled. Most clusters are unique to one of the mutant strains. Only cluster 8 and 15 show similar patterns across the 3 models, and clusters 7 and 14 are similar in the polyQ models but not HSA-AR.</p>", "links"=>[], "tags"=>["neuroscience/neurobiology of disease and regeneration", "neurological disorders/neurogenetics", "neurological disorders/neuromuscular diseases", "neurological disorders/spinal disorders"], "article_id"=>498688, "categories"=>["Neuroscience"], "users"=>["Kaiguo Mo", "Zak Razak", "Pengcheng Rao", "Zhigang Yu", "Hiroaki Adachi", "Masahisa Katsuno", "Gen Sobue", "Andrew P. Lieberman", "J. Timothy Westwood", "D. Ashley Monks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012922.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hierarchical_cluster_analysis_of_gene_expression_in_the_3_mouse_models_/498688", "title"=>"Hierarchical cluster analysis of gene expression in the 3 mouse models.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-23 02:24:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/828240"], "description"=>"<p>Diagram representing the number of genes whose expression differed from WT controls for each mutant strain (HSA-AR, AR97Q, AR113Q), and the number of such genes shared by each model. Notably, the overlap between HSA-AR and either of the polyQ models was similar to the overlap between the polyQ AR samples. Gene numbers were obtained by examining gene lists generated by a 2-fold, p≤0.05 criterion.</p>", "links"=>[], "tags"=>["diagrams", "microarray"], "article_id"=>498601, "categories"=>["Neuroscience"], "users"=>["Kaiguo Mo", "Zak Razak", "Pengcheng Rao", "Zhigang Yu", "Hiroaki Adachi", "Masahisa Katsuno", "Gen Sobue", "Andrew P. Lieberman", "J. Timothy Westwood", "D. Ashley Monks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012922.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Venn_diagrams_of_microarray_results_by_mouse_model_/498601", "title"=>"Venn diagrams of microarray results by mouse model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-23 02:23:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/828407"], "description"=>"<p>Functional analysis of regulated genes was performed using Functional Annotation Tool (DAVID Bioinformatics Resources) according to GO term (biological process, molecular function and cellular component) on several clusters: cluster 8 which was down in all models, cluster 15 which was up in all models, clusters 2 and 7 which were down in polyQ models only, cluster 14 which was up in polyQ models only, cluster 4 which was up only in HSA-AR and clusters 10 and 11 which were up only in HSA-AR.</p>", "links"=>[], "tags"=>["distributions", "regulated", "genes", "clusters", "annotation", "visualization"], "article_id"=>498759, "categories"=>["Neuroscience"], "users"=>["Kaiguo Mo", "Zak Razak", "Pengcheng Rao", "Zhigang Yu", "Hiroaki Adachi", "Masahisa Katsuno", "Gen Sobue", "Andrew P. Lieberman", "J. Timothy Westwood", "D. Ashley Monks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012922.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_distributions_of_regulated_genes_in_some_clusters_by_Database_for_Annotation_Visualization_and_Integrated_Discovery_DAVID_analysis_/498759", "title"=>"Functional distributions of regulated genes in some clusters by Database for Annotation Visualization and Integrated Discovery (DAVID) analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-23 02:25:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/412439", "https://ndownloader.figshare.com/files/412454", "https://ndownloader.figshare.com/files/412471", "https://ndownloader.figshare.com/files/412489", "https://ndownloader.figshare.com/files/412499", "https://ndownloader.figshare.com/files/412515"], "description"=>"<div><h3>Background</h3><p>Emerging evidence implicates altered gene expression 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 disease. The mouse models included a polyglutamine expanded (polyQ) AR knock-in model (AR113Q), a polyQ AR transgenic model (AR97Q), and a transgenic mouse that overexpresses wild type AR solely in skeletal muscle (HSA-AR). HSA-AR mice were included because they substantially reproduce the KD/SBMA phenotype despite the absence of polyQ AR.</p><h3>Methodology/Principal Findings</h3><p>We performed microarray analysis of lower hindlimb muscles taken from these three models relative to wild type controls using high density oligonucleotide arrays. All microarray comparisons were made with at least 3 animals in each condition, and only those genes having at least 2-fold difference and whose coefficient of variance was less than 100% were considered to be differentially expressed. When considered globally, there was a similar overlap in gene changes between the 3 models: 19% between HSA-AR and AR97Q, 21% between AR97Q and AR113Q, and 17% between HSA-AR and AR113Q, with 8% shared by all models. 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, muscle atrophy and myogenesis. We additionally measured changes similar to those observed in skeletal muscle of a mouse model of Huntington's Disease, and to those common to muscle atrophy from diverse causes.</p><h3>Conclusions/Significance</h3><p>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.</p></div>", "links"=>[], "tags"=>["microarray", "skeletal", "models", "kennedy", "bulbar", "muscular", "atrophy"], "article_id"=>141479, "categories"=>["Neuroscience"], "users"=>["Kaiguo Mo", "Zak Razak", "Pengcheng Rao", "Zhigang Yu", "Hiroaki Adachi", "Masahisa Katsuno", "Gen Sobue", "Andrew P. Lieberman", "J. Timothy Westwood", "D. Ashley Monks"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0012922.s001", "https://dx.doi.org/10.1371/journal.pone.0012922.s002", "https://dx.doi.org/10.1371/journal.pone.0012922.s003", "https://dx.doi.org/10.1371/journal.pone.0012922.s004", "https://dx.doi.org/10.1371/journal.pone.0012922.s005", "https://dx.doi.org/10.1371/journal.pone.0012922.s006"], "stats"=>{"downloads"=>6, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Microarray_Analysis_of_Gene_Expression_by_Skeletal_Muscle_of_Three_Mouse_Models_of_Kennedy_Disease_Spinal_Bulbar_Muscular_Atrophy/141479", "title"=>"Microarray Analysis of Gene Expression by Skeletal Muscle of Three Mouse Models of Kennedy Disease/Spinal Bulbar Muscular Atrophy", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-09-23 00:24:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/828450"], "description"=>"<p>Complete gene lists resulting from microarray analysis of each model were separately analyzed with DAVID and the resulting KEGG pathways and associated p-values of obtaining these pathways by chance are represented. The number of hits was determined from the gene lists manually.</p>", "links"=>[], "tags"=>["pathways"], "article_id"=>498808, "categories"=>["Neuroscience"], "users"=>["Kaiguo Mo", "Zak Razak", "Pengcheng Rao", "Zhigang Yu", "Hiroaki Adachi", "Masahisa Katsuno", "Gen Sobue", "Andrew P. Lieberman", "J. Timothy Westwood", "D. Ashley Monks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012922.t003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_KEGG_analysis_of_gene_pathways_for_shared_clusters_/498808", "title"=>"KEGG analysis of gene pathways for shared clusters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-23 02:26:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/828494"], "description"=>"<p>All samples were compared with their WT controls to evaluate fold change. The expression of each test gene was normalized to the level of GAPDH within each sample prior to comparisons between samples. Each group represents samples from 3 mice.</p>", "links"=>[], "tags"=>["microarray", "experiments", "qrt-pcr"], "article_id"=>498852, "categories"=>["Neuroscience"], "users"=>["Kaiguo Mo", "Zak Razak", "Pengcheng Rao", "Zhigang Yu", "Hiroaki Adachi", "Masahisa Katsuno", "Gen Sobue", "Andrew P. Lieberman", "J. Timothy Westwood", "D. Ashley Monks"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012922.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Validation_of_the_results_of_microarray_experiments_by_qRT_PCR_analysis_/498852", "title"=>"Validation of the results of microarray experiments by qRT-PCR analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-23 02:27:32"}

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