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K. Wu, X. Li, S. F. Hamm-Alvarez; Genes Encoding Salivary Gland-Enriched Proteins Exhibit Increased Expression in Diseased Lacrimal Glands From Male NOD Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2450.
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Expression of cellular proteins at the wrong time or in the wrong location may lead to production of neoautoantigens which may underlie the autoimmune disorders seen both in Sjögren’s syndrome (SjS) patients and in the NOD mouse model. Autoantibodies against Amylase 1 (Amy1) have been detected in some SjS patients. Induced expression and altered post-translational processing of parotid secretory protein (PSP) were previously observed in submandibular gland (SMG) of NOD mice. The purpose of this study was to investigate the gene expression in the lacrimal gland (LG) of Amy1, PSP and several other genes implicated in autoimmunity in the NOD mouse model.
Gene expression was investigated by real-time RT-PCR. Total RNA pools for the experiments were purified from LGs and SMGs of male NOD, NOD SCID and BALB/c mice at 4 and/or 12 weeks of age.
The expressions of Amy1 and PSP were investigated by real-time RT-PCR in LGs and SMGs of NOD mice at 12 weeks of age in comparison with the BALB/c controls. The mRNA levels of Amy1 and PSP in the LGs of NOD mice were 36.7-fold and 160.2-fold respectively as high as in the control LGs. The mRNA levels of three kallikrein family members (mGKs) were also investigated. The fold changes of mRNA levels of mGK6, mGK11, and mGK26 in NOD mice at 12 weeks of age compared to the controls were 13.3, 271.4 and 178.6 respectively. In contrast, the mRNA levels in SMGs between the two strains were close. Additional analyses revealed that the expression levels of all the genes studied in LG were much higher in 12-week than in 4-week old mice of the same strain. There was no major difference in the mRNA abundance of Amy1 and PSP between the two strains at 4 weeks of age, whereas the three mGKs in the LGs of NOD mice already showed higher mRNA abundance than in the BALB/c control. Furthermore, immune-compromised matched NOD SCID mice showed similar gene expression patterns to 12-week old NOD mice.
The elevated expressions of PSP, Amy1 and the three mGKs are strain-specific, age-dependent, autoimmunity-independent and correlated with the immune cell infiltration in the LG of male NOD mouse. The detection of increased PSP in the LG of male NOD mice that precedes any increase in SMG is consistent with the earlier onset of lymphocytic infiltration in the LG than that in the SMG of the male mice observed in our laboratory. These changes in mRNA abundance implicate de-regulated transcription and an altered cellular protein population, and thus may constitute a key factor for neoautoantigen presentation in the LG of male NOD mouse.
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