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Open Access Research article

The influence of the NOD Nss1/Idd5 loci on sialadenitis and gene expression in salivary glands of congenic mice

Trond Ove R Hjelmervik12*, Anna-Karin Lindqvist3, Kjell Petersen4, Martina Johannesson5, Anne-Kristin Stavrum6, Åsa Johansson7, Roland Jonsson2, Rikard Holmdahl7 and Anne Isine Bolstad1

Author Affiliations

1 Department of Oral Sciences-Periodontology, Faculty of Dentistry, University of Bergen, Årstadveien, N-5009 Bergen, Norway

2 Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Haukelandsveien, N-5021 Bergen, Norway

3 Cartela AB, Scheelevägen, SE-220 07 Lund, Sweden

4 Computational Biology Unit, Bergen Center of Computational Biology, University of Bergen, Høyteknologisenteret, Thormøhlensgate, N-5008 Bergen, Norway

5 Psychiatric Genetics, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK

6 Department of Clinical Medicine, University of Bergen, Haukeland University Hospital, Jonas Lies vei, N-5020 Bergen, Norway

7 Medical Inflammation Research, University of Lund, Sölvegatan, 221 84 Lund, Sweden

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Arthritis Research & Therapy 2007, 9:R99  doi:10.1186/ar2300

Published: 27 September 2007

Abstract

The nonobese diabetic (NOD) Nss1 and Idd5 loci have been associated with sialadenitis development in mice. In this study the NOD Nss1 and Idd5 loci were backcrossed onto the healthy control strain B10.Q by using the speed congenic breeding strategy, resulting in three congenic strains: B10.Q.Nss1, B10.Q.Nss1/Idd5 heterozygous and B10.Q.Nss1/Idd5 homozygous. We investigated the effects of the Nss1 and Idd5 loci on sialadenitis and gene expression in NOD congenic mice. One submandibular salivary gland from each mouse was used for histological analysis of sialadenitis, whereas the contralateral salivary gland was used for gene expression profiling with the Applied Biosystems Mouse Genome Survey chip v.1.0. The results were validated using quantitative reverse transcriptase PCR. The NOD Nss1 and Idd5 loci had clear influence on the onset and progression of sialadenitis in congenic mice. Double congenic mice exhibited the most severe phenotype. We successfully identified several genes that are located in the NOD congenic regions to be differentially expressed between the congenic strains and the control strain. Several of these were found to be co-regulated, such as Stat1, complement component C1q genes and Tlr12. Also, a vast contingency of interferon-regulated genes (such as Ltb, Irf7 and Irf8) and cytokine and chemokine genes (such as Ccr7 and Ccl19) were differentially expressed between the congenic strains and the control strain. Over-representation of inflammatory signalling pathways was observed among the differentially expressed genes. We have found that the introgression of the NOD loci Nss1 and Idd5 on a healthy background caused sialadenitis in NOD congenic mouse strains, and we propose that genes within these loci are important factors in the pathogenesis. Furthermore, gene expression profiling has revealed several differentially expressed genes within and outside the NOD loci that are similar to genes found to be differentially expressed in patients with Sjögren's syndrome, and as such are interesting candidates for investigation to enhance our understanding of disease mechanisms and to develop future therapies.