title: Differential gene expression in the salivary gland during development and onset of xerostomia in Sjögren's syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouse.
abstract: BACKGROUND
  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 Sjögren'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.
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA. Nguyen@pathology.ufl.edu
authors.forename: Cuong Q
authors.initials: CQ
authors.lastname: Nguyen
authors.forename: Ashok
authors.initials: A
authors.lastname: Sharma
authors.forename: Byung Ha
authors.initials: BH
authors.lastname: Lee
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.forename: Richard A
authors.initials: RA
authors.lastname: McIndoe
authors.forename: Ammon B
authors.initials: AB
authors.lastname: Peck
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000254:growth & development* / Q000502:physiology*; D012859:Sjogren's Syndrome / Q000235:genetics*; D014987:Xerostomia / Q000235:genetics*
chemical_list: D012333:RNA, Messenger