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Doctoral Thesis
DOI
10.11606/T.42.2009.tde-08072009-122546
Document
Author
Full name
Luciana Carla Oliva Marques Peters
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Franco, Marcelo de (President)
Câmara, Niels Olsen Saraiva
Keller, Alexandre de Castro
Negro, Sonia Jancar
Oliveira, Silvio Luis de
Title in Portuguese
Identificação dos loci reguladores da intensidade da resposta inflamatória aguda envolvidos no desenvolvimento da artrite induzida por pristane em camundongos selecionados geneticamente.
Keywords in Portuguese
Loci de traço quantitativo
Artrite
Camundongos
Expressão gênica
Imunologia
Inflamação
Microarray e qPCR
Seleção genética
Abstract in Portuguese
Camundongos AIRmax e AIRmin homozigotos para os alelos R e S do gene Slc11a1 foram avaliados para susceptibilidade à artrite induzida por pristane (PIA). A presença do alelo S aumentou a incidência e a gravidade nos AIRmax, sugerindo que o gene Slc11a1, ou outro próximo, esteja interagindo com os loci de resposta inflamatória na modulação de PIA. Para identificar estes loci foram realizados estudos de associação genótipo-fenótipo e de expressão gênica global. Os RNAs das patas dos animais foram isolados após 180 dias da indução por pristane. As análises de expressão gênica global foram realizadas usando a plataforma Codelink (36k genes), cujos resultados foram validados por PCR em tempo real. Os estudos de associação foram realizados através da análise de polimorfismo de microssatélites pelo programa MapManager. Foram identificadas duas regiões nos cromossomos 1 e 11. Um número grande de genes diferencialmente expressos foi verificado nos animais AIRmax SS cujos temas biológicos significativamente sobre-representados foram a resposta inflamatória e quimiotaxia. Os camundongos AIRmax SS também possuem uma ativação maior dos genes Ccl3, Ccl7, C3ar1, Il10, Stat3, Tirap, Trem 1, Trem 3, Mefv, Ptx3, Chi3l3 e Kras. Alguns desses genes co-localizam com regiões previamente mapeadas nos cromossomos 1 e 11.
Title in English
Identification of acute inflammatory response loci involved on pristane-induced arthritis development in mice genetically selected.
Keywords in English
Arthritis
Gene expression
Immunology
Inflammation
Mice
Microarray and qPCR
Quantitative trait Loci
Abstract in English
AIRmax and AIRmin mice homozygous for Slc11a1 R and S allele were evaluated for pristane-induced arthritis (PIA) susceptibility. The presence of S allele increased the incidence and the arthritis severity in ARmax mice, suggesting that Slc11a1 or other closed-linked gene interacts with inflammatory loci to modulate PIA. In order to identify inflammatory modifier loci modulating experimental arthritis development, genotype-phenotype association studies and global gene expression analyses were performed. Mice received i.p. injections of pristane and the paw RNAs were isolated at day 180. Global gene expression analysis was performed on Codelink bioarrays (36k genes) and validated by real time PCR. The microsatellite polymorphism analyses were performed using MapManager program. Two regions on chromosomes 1 and 11 were identified. Higher number of differentially-expressed genes were detected in AIRmax SS subline, which significant over-represented biological themes were related to inflammatory response and chemotaxis. Susceptible AIRmax SS mice also display high up-regulation of Ccl3, Ccl7, C3ar1, Il10, Stat3, Tirap, Trem 1, Trem 3, Mefv, Ptx3, Chi3l3 e Kras genes. Some of them co-localize with previously identified regions mapped on chromosomes 1 and 11.
 
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Publishing Date
2009-08-17
 
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