Genomic view of systemic autoimmunity in MRLlpr mice

J. Liu, G. Karypis, K. L. Hippen, A. L. Vegoe, Phillip Ruiz, G. S. Gilkeson, T. W. Behrens

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)156-168
Number of pages13
JournalGenes and Immunity
Volume7
Issue number2
DOIs
StatePublished - Mar 1 2006

Fingerprint

Autoimmunity
Genes
Kidney
Spleen
Gene Components
Antigen Presentation
Chemokines
Systemic Lupus Erythematosus
Autoantibodies
Interferons
Flow Cytometry
Membrane Proteins
Transcription Factors
Genome
Pathology
Cytokines
Inflammation
Gene Expression
Messenger RNA
Serum

Keywords

  • Microarray gene expression analysis
  • MRLlpr mice
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Liu, J., Karypis, G., Hippen, K. L., Vegoe, A. L., Ruiz, P., Gilkeson, G. S., & Behrens, T. W. (2006). Genomic view of systemic autoimmunity in MRLlpr mice. Genes and Immunity, 7(2), 156-168. https://doi.org/10.1038/sj.gene.6364286

Genomic view of systemic autoimmunity in MRLlpr mice. / Liu, J.; Karypis, G.; Hippen, K. L.; Vegoe, A. L.; Ruiz, Phillip; Gilkeson, G. S.; Behrens, T. W.

In: Genes and Immunity, Vol. 7, No. 2, 01.03.2006, p. 156-168.

Research output: Contribution to journalArticle

Liu, J, Karypis, G, Hippen, KL, Vegoe, AL, Ruiz, P, Gilkeson, GS & Behrens, TW 2006, 'Genomic view of systemic autoimmunity in MRLlpr mice', Genes and Immunity, vol. 7, no. 2, pp. 156-168. https://doi.org/10.1038/sj.gene.6364286
Liu J, Karypis G, Hippen KL, Vegoe AL, Ruiz P, Gilkeson GS et al. Genomic view of systemic autoimmunity in MRLlpr mice. Genes and Immunity. 2006 Mar 1;7(2):156-168. https://doi.org/10.1038/sj.gene.6364286
Liu, J. ; Karypis, G. ; Hippen, K. L. ; Vegoe, A. L. ; Ruiz, Phillip ; Gilkeson, G. S. ; Behrens, T. W. / Genomic view of systemic autoimmunity in MRLlpr mice. In: Genes and Immunity. 2006 ; Vol. 7, No. 2. pp. 156-168.
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