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 journalArticlepeer-review

59 Scopus citations


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
Issue number12
StatePublished - Dec 2 2006
Externally publishedYes


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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


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