The Department of Biomedicine

BBB Seminar: Ammon B. Peck

Identification of candidate genes and signaling pathways in autoimmunity using genomic microarrays

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Ammon B. Peck, Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA

The Sjögren syndrome (SS) is one of the most common autoimmune diseases. Early clinical manifestations of SS are primarily decreased tear and saliva secretion, leading to dry eyes and dry mouth syndromes, but in its later stages, can become systemic, even resulting in B cell lymphomas. The use of new animal models, coupled with new technologies such as genomics and proteomics, is providing insights into the pathogenesis, genetic predisposition, and possibly, early diagnosis. 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 SS-like disease on SS-non-susceptible C57BL/6 mice. In an attempt to define the molecular bases underlying this disease, we have carried out a study utilizing microarray technology. Using oligonucleotide microarrays, temporal gene expression profiles of lacrimal and salivary glands were generated for C57BL/6.NOD-Aec1Aec2 mice covering the development and early onset of disease. Analyses using Linear Models for Microarray Analysis package and B-statistics identified 552 genes in the lacrimal glands and 480 genes in the salivary gland as being differentially expressed during disease development. Using pair-wise analyses, additional genes, many of which correspond to known immuno-pathophysiological mechanisms suspected to underlie disease, were identified as differentially expressed both temporally and quantitatively. Selecting a few families of genes, e.g., cystatins, cathepsins, metalloproteinases, lipocalins, complement, kallikreins, tumor necrosis factors, chemokines and cytokines, it was noted that only a limited number of such family members showed differential expressions, suggesting restricted glandular expressions. Utilizing these genes, several pathways of interactive genes have been constructed for several cellular events, thereby permitting identification of multiple sets of genes of interest whose expressions and expression profiles may correlate with molecular mechanisms, signaling pathways and autoimmune processes involved in the development and onset of SS. Thus, temporal microarray data permits model building that may provide new insights into the underlying cause of this autoimmune disease.

Chair: Silke Appel (silke.appel@gades.uib.no), The Gade Institute