Early pathogenic events associated with Sjögren's syndrome (SjS)-like disease of the nod mouse using microarray analysis

Smruti Y. Killedar, Sarah E. Eckenrode, Richard A McIndoe, Jin-Xiong She, Cuong Q. Nguyen, Ammon B. Peck, Seunghee R. Cha

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Recently, we reported development of the C57BL/6.NOD-Aec1Aec2 mouse carrying two genetic intervals derived from the NOD mouse. These two genetic regions confer full Sjögren's syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. The current study was undertaken to apply microarray technology to define the molecular basis underlying onset of SjS-disease in C57BL/6.NOD-Aec1Aec2 mice. Using oligonucleotide microarrays, gene expression profiles of submandibular glands derived from 8- to 12-week-old C57BL/6.NOD-Aec1Aec2 mice and 8-week-old C57BL/6 mice were performed for comparison. Significant differential expressions were determined using the Mann-Whitney U test. Hybridizations using submandibular cDNA probes revealed 75 differentially expressed genes at 8 weeks and 105 differentially expressed genes at 12 weeks of age in C57BL/6.NOD-Aec1Aec2 mice compared to 8-week-old C57BL/6 mice. These genes were related generally to basic cellular activities such as transcription, translation, DNA replication, and protein folding. During the predisease phase, genes upregulated encode proteins associated with the IFN-gamma signal-transduction-pathway (Jak/Stat1), TLR-3 (Irf3 and Traf6) and apoptosis (casp11 and casp3), indicative of chronic proinflammatory stimuli, especially IL-1. Between 8 and 12 weeks of age, sets of clustered genes were upregulated that are associated with adaptive immune responses, especially B cell activation, proliferation and differentiation (Baffr, Taci, Bcma, Blys, April, CD70, CD40L, Traf1, Traf3, Pax5, c-Jun, Elk1 and Nf-kB), and neural receptors (Taj/Troy). Altered gene expressions of TLR3 and TNF-superfamily- receptors and ligands during this early phase of SjS suggest a possible viral etiology in the altered glandular homeostasis with an upregulated, possibly overstimulated, B-lymphocyte activation in the early autoimmune response present in the submandibular glands. The importance of NF-κB as a critical signal transduction pathway is also suggested but its link is not yet clear.

Original languageEnglish (US)
Pages (from-to)1243-1260
Number of pages18
JournalLaboratory Investigation
Volume86
Issue number12
DOIs
StatePublished - Dec 2 2006

Fingerprint

Inbred NOD Mouse
Microarray Analysis
Inbred C57BL Mouse
Submandibular Gland
Genes
Signal Transduction
B-Lymphocytes
Tumor Necrosis Factors
CD40 Ligand
Protein Folding
Adaptive Immunity
Sensory Receptor Cells
Lymphocyte Activation
Nonparametric Statistics
Oligonucleotide Array Sequence Analysis
DNA Replication
Autoimmunity
Interleukin-1
Transcriptome
Cell Differentiation

Keywords

  • Autoimmunity
  • Microarray
  • NOD mouse
  • Salivary gland
  • Sjögren's syndrome

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Early pathogenic events associated with Sjögren's syndrome (SjS)-like disease of the nod mouse using microarray analysis. / Killedar, Smruti Y.; Eckenrode, Sarah E.; McIndoe, Richard A; She, Jin-Xiong; Nguyen, Cuong Q.; Peck, Ammon B.; Cha, Seunghee R.

In: Laboratory Investigation, Vol. 86, No. 12, 02.12.2006, p. 1243-1260.

Research output: Contribution to journalArticle

Killedar, Smruti Y. ; Eckenrode, Sarah E. ; McIndoe, Richard A ; She, Jin-Xiong ; Nguyen, Cuong Q. ; Peck, Ammon B. ; Cha, Seunghee R. / Early pathogenic events associated with Sjögren's syndrome (SjS)-like disease of the nod mouse using microarray analysis. In: Laboratory Investigation. 2006 ; Vol. 86, No. 12. pp. 1243-1260.
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