Genomic view of systemic autoimmunity in MRLlpr mice
| Autor: | Timothy W. Behrens, Keli L. Hippen, Jiabin Liu, P. Ruiz, George Karypis, Amanda L. Vegoe, Gary S. Gilkeson |
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| Rok vydání: | 2006 |
| Předmět: |
Candidate gene
Mice Inbred MRL lpr Immunology Autoimmunity Enzyme-Linked Immunosorbent Assay Disease Biology medicine.disease_cause Kidney Interferon-gamma Mice Genetics medicine Animals Lupus Erythematosus Systemic Gene Genetics (clinical) Oligonucleotide Array Sequence Analysis Lupus erythematosus Genome Gene Expression Profiling Membrane Proteins medicine.disease Flow Cytometry Gene expression profiling Mice Inbred C57BL medicine.anatomical_structure Renal pathology Disease Progression Female Chemokines Spleen Transcription Factors |
| Zdroj: | Genes and immunity. 7(2) |
| ISSN: | 1466-4879 |
| Popis: | MRLlpr mice develop spontaneous systemic autoimmunity with many hallmarks of the human disease systemic lupus erythematosus. Although a variety of genes have been implicated in this model, disease pathogenesis is still poorly understood. In an effort to identify novel genes and pathways, we performed genome-wide mRNA expression analysis in the spleens and kidneys of MRLlpr mice throughout the disease course. Samples were collected from cohorts of C57BL/6, MRL+/+ and MRLlpr mice, and profiled by flow cytometry and gene expression microarrays. Serum autoantibodies and renal pathology were studied in parallel. We identified 236 genes in MRLlpr spleen that showed significant threefold or greater changes in expression between 6 and 20 weeks. Of interest, a number of interferon-responsive genes were expressed early, and remained dysregulated throughout the disease course. Many chemokines, cell surface proteins, transcription factors and cytokines, including IFN-gamma, also showed altered expression as disease progressed. Analysis of kidneys indicated the presence of severe inflammation that coincided with evidence for changes in kidney function and elevated expression of IFN-inducible genes, complement components and antigen presentation genes. These data provide a unique genomic view of the progression to fatal autoimmunity in MRLlpr mice, and provide new candidate genes and pathways to explore. |
| Databáze: | OpenAIRE |
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