Differential gene expression in the salivary gland during development and onset of xerostomia in Sj??gren's syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouse.
MetadataShow full item record
AbstractINTRODUCTION: Recently, we reported the development of the C57BL/6.NOD-Aec1Aec2 mouse that carries two genetic intervals derived from the non-obese diabetic (NOD) mouse capable of conferring Sj??gren's syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. In an attempt to define the molecular bases underlying the onset of stomatitis sicca (xerostomia) in this C57BL/6.NOD-Aec1Aec2 mouse model, we have carried out a study using genomic microarray technology. METHODS: By means of oligonucleotide microarrays, gene expression profiles of salivary glands at 4, 8, 12, 16, and 20 weeks of age were generated for C57BL/6.NOD-Aec1Aec2 male mice. Using Linear Models for Microarray Analysis and B-statistics software, 480 genes were identified as being differentially expressed (P < 0.01 and Q < 0.0001) during the development of SjS-like disease in the salivary glands. RESULTS: The 480 genes could be arranged into four clusters, with each cluster defining a unique pattern of temporal expression, while the individual genes within each cluster could be grouped according to related biological functions. By means of pair-wise analysis, temporal changes in transcript expressions provided profiles indicating that many additional genes are differentially expressed at specific time points during the development of disease. Multiple genes reportedly showing an association with autoimmunity and/or SjS, in either humans or mouse models, were found to exhibit differential expressions, both quantitatively and temporally. Selecting various families of genes associated with specific functions (for example, antibody production, complement, and chemokines), we noted that only a limited number of family members showed differential expressions and these correlated with specific phases of disease. CONCLUSIONS: Taking advantage of known functions of these genes, investigators can construct interactive gene pathways, leading to modeling of possible underlying events inducing salivary gland dysfunction. Thus, these different approaches to analyzing microarray data permit the identification of multiple sets of genes of interest whose expressions and expression profiles may correlate with molecular mechanisms, signaling pathways, and/or immunological processes involved in the development and onset of SjS.
CitationArthritis Res Ther. 2009 Apr 20; 11(2):R56
- Differential gene expressions in the lacrimal gland during development and onset of keratoconjunctivitis sicca in Sjögren's syndrome (SJS)-like disease of the C57BL/6.NOD-Aec1Aec2 mouse.
- Authors: Nguyen CQ, Sharma A, She JX, McIndoe RA, Peck AB
- Issue date: 2009 Mar
- Early pathogenic events associated with Sjögren's syndrome (SjS)-like disease of the NOD mouse using microarray analysis.
- Authors: Killedar SJ, Eckenrode SE, McIndoe RA, She JX, Nguyen CQ, Peck AB, Cha S
- Issue date: 2006 Dec
- Gene expression profiling of early-phase Sjögren's syndrome in C57BL/6.NOD-Aec1Aec2 mice identifies focal adhesion maturation associated with infiltrating leukocytes.
- Authors: Peck AB, Saylor BT, Nguyen L, Sharma A, She JX, Nguyen CQ, McIndoe RA
- Issue date: 2011 Jul 29
- Identification of possible candidate genes regulating Sjögren's syndrome-associated autoimmunity: a potential role for TNFSF4 in autoimmune exocrinopathy.
- Authors: Nguyen CQ, Cornelius JG, Cooper L, Neff J, Tao J, Lee BH, Peck AB
- Issue date: 2008
- Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model.
- Authors: Horvath S, Nazmul-Hossain AN, Pollard RP, Kroese FG, Vissink A, Kallenberg CG, Spijkervet FK, Bootsma H, Michie SA, Gorr SU, Peck AB, Cai C, Zhou H, Wong DT
- Issue date: 2012 Nov 1