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http://hdl.handle.net/1956/2677
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| Tittel: | The influence of the NOD Nss1/Idd5 loci on sialadenitis and gene expression in salivary glands of congenic mice |
| Forfattere: | Hjelmervik, Trond Ove R.
Linqvist, Anne-Karin
Petersen, Kjell
Johannesson, Martina
Stavrum, Anne-Kristin
Johansson, Åsa
Jonsson, Roland
Holmdah, Rikard
Bolstad, Anne Isine |
| Dato: | 27-Sep-2007 |
| Forlag: | BioMed Central |
| Sitering: | Arthritis Research & Therapy 2007, 9: |
| Sammendrag: | 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. |
| URI: | http://dx.doi.org/10.1186/ar2300
http://hdl.handle.net/1956/2677 |
| Vises i samlingene: | Department of Oral Sciences
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