Candidate chromosome 1 disease susceptibility genes for Sjogren's syndrome xerostomia are narrowed by novel NOD.B10 congenic mice

Mongini, Patricia K. A.; Kramer, Jill M.; Ishikawa, Tomo-o; Herschman, Harvey; Esposito, Donna

doi:10.1016/j.clim.2014.03.012

Cited by 5 publications

(5 citation statements)

References 63 publications

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“…NOD.B10-H2 b model was also used to test how sex hormones influence SjS development, where removal of ovaries from NOD.B10-H2 b mice accelerated the development of disease while sex hormone replacement prevented the symptoms [64]. Interestingly, a conditional knockout mouse for tissue-specific disruption of the cyclooxgenase (Cox-2) gene developed by backcrossing NOD.B10-H2 b mice and Cox-2 flox/flox mice which bear a floxed Cox-2 gene on a mixed 129/B6 background failed to manifest xerostomia [65, 66]. Further analyses delineated candidate autoimmune exocrinopathy (Aec) 2 alleles on chromosome 1 are needed for SS xerostomia [54, 66].…”

Section: Mouse Modelsmentioning

confidence: 99%

“…Interestingly, a conditional knockout mouse for tissue-specific disruption of the cyclooxgenase (Cox-2) gene developed by backcrossing NOD.B10-H2 b mice and Cox-2 flox/flox mice which bear a floxed Cox-2 gene on a mixed 129/B6 background failed to manifest xerostomia [65, 66]. Further analyses delineated candidate autoimmune exocrinopathy (Aec) 2 alleles on chromosome 1 are needed for SS xerostomia [54, 66]. In addition, the beneficial effects of epigallocatechin-3-gallate(EGCG), polyphenols extracted from green tea leaves, on SjS was reported both in NOD mice and NOD.B10-H2 b mice [67, 68].…”

Section: Mouse Modelsmentioning

confidence: 99%

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Mouse Models of Primary Sjogren’s Syndrome

Park¹,

Gauna²,

Cha

2015

CPD

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Sjögren’s syndrome (SjS) is a chronic autoimmune disorder characterized by immune cell infiltration and progressive injury to the salivary and lacrimal glands. As a consequence, patients with SjS develop xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). SjS is the third most common rheumatic autoimmune disorder, affecting 4 million Americans with over 90% of patients being female. Current diagnostic criteria for SjS frequently utilize histological examinations of minor salivary glands for immune cell foci, serology for autoantibodies, and dry eye evaluation by corneal or conjunctival staining. SjS can be classified as primary or secondary SjS, depending on whether it occurs alone or in association with other systemic rheumatic conditions, respectively. Clinical manifestations typically become apparent when the disease is relatively advanced in SjS patients, which poses a challenge for early diagnosis and treatment of SjS. Therefore, SjS mouse models, because of their close resemblance to the human SjS, have been extremely valuable to identify early disease markers and to investigate underlying biological and immunological dysregulations. However, it is important to bear in mind that no single mouse model has duplicated all aspects of SjS pathogenesis and clinical features, mainly due to the multifactorial etiology of SjS that includes numerous susceptibility genes and environmental factors. As such, various mouse models have been developed in the field to try to recapitulate SjS. In this review, we focus on recent mouse models of primary SjS and describe them under three categories of spontaneous, genetically engineered, and experimentally induced development of SjS-like disease. In addition, we discuss future perspectives of SjS mouse models highlighting pros and cons of utilizing mouse models and demands for improved models.

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Section: Mouse Modelsmentioning

confidence: 99%

Section: Mouse Modelsmentioning

confidence: 99%

Mouse Models of Primary Sjogren’s Syndrome

Park¹,

Gauna²,

Cha

2015

CPD

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“…Although the cause of xerostomia in SS is not completely understood, autoantibodies, apoptosis of glandular tissue, polymorphisms in inflammatory genes, and lymphocytic infiltration of salivary tissue may all contribute to loss of saliva [27–30]. To determine whether Opn Tg animals exhibit decreased salivary flow, we assayed production of stimulated saliva following intraperitoneal injection with the parasympathetic agonist, pilocarpine.…”

Section: Resultsmentioning

confidence: 99%

The osteopontin transgenic mouse is a new model for Sjögren's syndrome

Husain-Krautter

Kramer

et al. 2015

Clinical Immunology

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Osteopontin (Opn) is a cytokine involved in both physiological and pathological processes, and is elevated in many autoimmune diseases. Sjögren’s syndrome (SS) is an autoimmune disease with a strong female predilection characterized by lymphocytic infiltration of exocrine glands. We hypothesized Opn contributes to SS pathogenesis. We examined an established SS model, and found increased Opn locally and systemically. Next, we examined Opn transgenic (Opn Tg) mice for evidence of SS. Opn Tg animals exhibited lymphocytic infiltration of salivary and lacrimal glands, and Opn co-localized with the infiltrates. Moreover, saliva production was reduced, and SS autoantibodies were observed in the serum of these mice. Finally, female Opn Tg mice showed more severe disease compared to males. Taken together, these data support a role for Opn in SS pathogenesis. We identify a new model of spontaneous SS that recapitulates the human disease in terms of sex predilection, histopathology, salivary deficits, and autoantibodies.

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“…The gene encoding PTGS2, also known as cyclooxygenase 2 (COX-2), is located on chromosome 1 ( Mongini et al, 2014 ). PTGS2 is a rate-limiting enzyme in the synthesis of prostaglandins (PGs), which catalyzes the metabolism of arachidonic acid (AA) into various PG products including the precursor prostaglandin H2 (PGH2) and leukotrienes (LTs) ( Wang et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Integration of metabolomics and network pharmacology to reveal the protective mechanism underlying Qibai Pingfei capsule on chronic obstructive pulmonary disease

Xie,

Liu,

Gao

et al. 2023

Front. Pharmacol.

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In this study, we have employed metabolomics technology in combination with network pharmacology to ascertain the key metabolites and hub genes. The objective was to explore the pathway of Qibai Pingfei Capsule (QBPF) in treating COPD through metabolomics. We identified 96 differential metabolites in the lung tissues of rats belonging to control and model groups, out of which 47 were observed to be critical (VIP >2, p < 0.05). Furthermore, 16 important differential metabolites were reversed after QBPF treatment. Using network pharmacology, we identified 176 core targets of 81 drug-active ingredients. Our comprehensive analysis of network pharmacology and metabolomics enabled us to identify a core target, prostaglandin-endoperoxide synthase 2 (PTGS2), and a core metabolic pathway for glutathione metabolism. Finally, the result of molecular docking showed that PTGS2 had strong binding activity to 18 compounds including Fumarine and Kaempferol, etc.. PTGS2 is a marker of ferroptosis, so we wanted to explore whether QBPF could inhibit ferroptosis in COPD. The results showed that ferroptosis was involved in the pathogenesis of COPD, and QBPF could inhibit the occurrence of ferroptosis. In conclusion, the mechanism of QBPF for treating COPD may be related to PTGS2 expression, glutathione metabolism and ferroptosis.

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Candidate chromosome 1 disease susceptibility genes for Sjogren's syndrome xerostomia are narrowed by novel NOD.B10 congenic mice

Cited by 5 publications

References 63 publications

Mouse Models of Primary Sjogren’s Syndrome

Mouse Models of Primary Sjogren’s Syndrome

The osteopontin transgenic mouse is a new model for Sjögren's syndrome

Integration of metabolomics and network pharmacology to reveal the protective mechanism underlying Qibai Pingfei capsule on chronic obstructive pulmonary disease

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