Identification of possible candidate genes regulating Sjögren's syndrome-associated autoimmunity: a potential role for TNFSF4 in autoimmune exocrinopathy
Open Access
- 1 January 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Arthritis Research & Therapy
- Vol. 10 (6), R137
- https://doi.org/10.1186/ar2560
Abstract
Introduction Sjogren syndrome (SjS) is a systemic autoimmune disease in which an immunological attack primarily against the salivary and lacrimal glands results in the loss of acinar cell tissue and function, leading to stomatitis sicca and keratoconjunctivitis sicca. In recent years, two genetic regions, one on chromosome 1 (designated autoimmune exocrinopathy 2 or Aec2) and the second on chromosome 3 (designated autoimmune exocrinopathy 1 or Aec1) derived from nonobese diabetic (NOD) mice, have been shown to be necessary and sufficient to replicate SjS-like disease in nonsusceptible C57BL/6 mice. Methods Starting with the SjS-susceptible C57BL/6-derived mouse, referred to as C57BL/6. NOD-Aec1Aec2, we generated a large set of recombinant inbred (RI) lines containing portions of Aec2 as a means of identifying more precisely the genetic elements of chromosome 1 responsible for disease development. Results Disease profiling of these RI lines has revealed that the SjS susceptibility genes of Aec2 lie within a region located at approximately 79 +/- 5 cM distal to the centromere, as defined by microsatellite markers. This chromosomal region contains several sets of genes known to correlate with various immunopathological features of SjS as well as disease susceptibility genes for both type 1 diabetes and systemic lupus erythematosus in mice. One gene in particular, tumor necrosis factor (ligand) superfamily member 4 (or Ox40 ligand), encoding a product whose biological functions correlate with both physiological homeostasis and immune regulations, could be a potential candidate SjS susceptibility gene. Conclusions These new RI lines represent the first step not only in fine mapping SjS susceptibility loci but also in identifying potential candidate SjS susceptibility genes. Identification of possible candidate genes permits construction of models describing underlying molecular pathogenic mechanisms in this model of SjS and establishes a basis for construction of specific gene knockout mice.This publication has 48 references indexed in Scilit:
- 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 mouseExperimental Eye Research, 2008
- Salivary gland tissue expression of interleukin‐23 and interleukin‐17 in Sjögren's syndrome: Findings in humans and miceArthritis & Rheumatism, 2008
- OX40 ligand shuts down IL-10-producing regulatory T cellsProceedings of the National Academy of Sciences of the United States of America, 2006
- Sjögren's Syndrome‐Like Disease of C57BL/6.NOD‐Aec1 Aec2 Mice: Gender Differences in Keratoconjunctivitis Sicca Defined by a Cross‐Over in the Chromosome 3 Aec1 LocusScandinavian Journal of Immunology, 2006
- Sjögren's syndrome in the NOD mouse model is an interleukin-4 time-dependent, antibody isotype-specific autoimmune diseaseJournal of Autoimmunity, 2006
- Detection of anti–type 3 muscarinic acetylcholine receptor autoantibodies in the sera of Sjögren's syndrome patients by use of a transfected cell line assayArthritis & Rheumatism, 2004
- Local Adeno-Associated Virus-Mediated Interleukin 10 Gene Transfer Has Disease-Modifying Effects in a Murine Model of Sjögren's SyndromeHuman Gene Therapy, 2003
- Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus GroupAnnals Of The Rheumatic Diseases, 2002
- Ro/SSA and La/SSB specific IgA autoantibodies in serum of patients with Sjogren's syndrome and systemic lupus erythematosusAnnals Of The Rheumatic Diseases, 1999
- Genetically Programmed Development of Salivary Gland Abnormalities in the NOD (Nonobese Diabetic)-scidMouse in the Absence of Detectable Lymphocytic Infiltration: A Potential Trigger for Sialoadenitis of NOD MiceClinical Immunology and Immunopathology, 1996