A novel NOD‐derived murine model of primary Sjögren's syndrome

Robinson, Carol; Yamachika, Shigeo; Bounous, Denise I.; Brayer, Jason; Jönsson, Roland; Holmdahl, Rikard; Peck, Ammon B.; Humphreys‐Beher, Michael G.

doi:10.1002/1529-0131(199801)41:1<150::aid-art18>3.3.co;2-k

Cited by 59 publications

(89 citation statements)

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“…To stimulate secretion of saliva, mice were given an intraperitoneal injection of isoproterenol (0.2 mg/100 g body weight) and pilocarpine (0.05 mg/100 g body weight) dissolved in saline [13,20]. Saliva samples were collected from each mouse for 10 min and their volumes determined.…”

Section: Methodsmentioning

confidence: 99%

IL‐4‐Dependent Effector Phase in Autoimmune Exocrinopathy as Defined by the NOD.IL‐4‐Gene Knockout Mouse Model of Sjögren's Syndrome

et al. 2001

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NOD mice manifest many features of autoimmune exocrinopathy (Sjögren's syndrome), a disease generally characterized by a chronic, progressive immunological attack against the exocrine tissues of the salivary and lacrimal glands. Previous studies using the NOD congenic partner strain, NOD.Igμnull, defined an important role for B lymphocytes in the development of xerostomia, implicating autoantibodies reactive with the acetylcholine muscarinic receptor (M3R) as the possible effector mechanism. In the present study, we have examined the impact of the cytokine, interleukin (IL)‐4, on autoimmune exocrinopathy by using the IL‐4 gene knockout (KO) NOD mouse strain, NOD.IL‐4−/−. Despite manifesting the physiological aberrations and marked leukocytic infiltration of the salivary glands characteristic of autoimmune xerostomia in NOD mice, the NOD.IL‐4−/− mice do not develop xerostomia. However, NOD.IL‐4−/− mice that received adoptively transferred T lymphocytes derived from NOD.Igμ−/− mice progress to xerostomia, thereby reversing the defect. While progression or lack of progression to xerostomia correlated with the ability of the NOD.IL‐4−/− mice to express detectable anti‐M3R autoantibodies, the precise mechanism of how IL‐4 influences the development of autoimmune xerostomia remains speculative.

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Section: Methodsmentioning

confidence: 99%

IL‐4‐Dependent Effector Phase in Autoimmune Exocrinopathy as Defined by the NOD.IL‐4‐Gene Knockout Mouse Model of Sjögren's Syndrome

et al. 2001

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“…These include autoimmune sialadenitis [30], autoimmune thyroiditis [31], hemolytic anemia [32], and prostatitis in male mice [33]. Accordingly, the NODderived mouse has been considered as a model of primary Sjogren syndrome, Guillain-Barré syndrome and multiple sclerosis [34][35][36].…”

Section: Cd25mentioning

confidence: 99%

Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system

et al. 2010

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NOD mice spontaneously develop insulin-dependent diabetes around 10-40 wk of age. Numerous immune gene variants contribute to the autoimmune process. However, genes that direct the autoimmune response toward b cells remain ill defined. In this study, we provide evidence that the Icos and Icosl genes contribute to the diabetes process. Protection from diabetes in ICOS À/À and ICOSL À/À NOD mice was unexpectedly associated with the development of an autoimmune disorder of the neuro-muscular system, characterized by myositis, sensory ganglionitis and, to a reduced extent, inflammatory infiltrates in the CNS. This syndrome was reproduced upon adoptive transfer of CD4 1 and CD8 1T cells from diseased donors to naïve NOD.scid recipients. Our data further show that protection from diabetes results from defective activation of autoimmune diabetogenic effector T cells in ICOS À/À NOD mice, whereas acceleration of diabetes in BDC2.5 ICOS À/À NOD mice is induced by a dominant defect in Treg. Taken together, our findings indicate that costimulation signals play a key role in regulating immune tolerance in peripheral tissues and that the ICOS/ICOSL costimulatory pathway influences the balance between Treg and diabetogenic effector T cells.

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“…Although the underlying reasons for these differences between male vs female mice are not known, they may reflect the different disease phenotypes exhibited by male and female mice, namely, that males have a more severe lacrimal gland disease while females have a more severe salivary gland disease (16,23,28).…”

Section: Aec1aec2c3mentioning

confidence: 99%

Development of Sjögren’s Syndrome in Nonobese Diabetic-Derived Autoimmune-Prone C57BL/6.NOD-Aec1Aec2 Mice Is Dependent on Complement Component-3

Nguyen

Kim

Cornelius

et al. 2007

The Journal of Immunology

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The role of complement in the etiology of Sjögren’s syndrome (SjS), a human autoimmune disease manifested primarily by salivary and lacrimal gland dysfunction resulting in dry mouth/dry eye syndrome, remains ill-defined. In the present study, we examined the role of complement component-3 (C3) using a newly constructed C3-gene knockout mouse, C57BL/6.NOD-Aec1Aec2.C3−/−. Inactivation of C3 in the parental C57BL/6.NOD-Aec1Aec2 strain, a model of primary SjS, resulted in a diminished or total absence of both preclinical and clinical manifestations during development and onset of disease, including reduced acinar cell apoptosis, reduced levels of caspase-3, lack of leukocyte infiltration of submandibular glands, reduced synthesis of disease-associated autoantibodies, maintenance of normal glandular architecture, and retention of normal saliva secretion. In addition, C57BL/6-NOD.Aec1Aec2.C3−/− mice did not exhibit increased numbers of marginal zone B cells, a feature of SjS-prone C57BL/6-NOD.Aec1Aec2 mice. Interestingly, C57BL/6-NOD.Aec1Aec2.C3−/− mice retained some early pathological manifestations, including activation of serine kinases with proteolytic activity for parotid secretory protein. This improvement in the clinical manifestations of SjS-like disease in C57BL/6.NOD-Aec1Aec2.C3−/− mice, apparently a direct consequence of C3 deficiency, supports a much more important role for complement in the adaptive autoimmune response than previously recognized, possibly implicating an essential role for innate immunity.

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A novel NOD‐derived murine model of primary Sjögren's syndrome

Cited by 59 publications

References 0 publications

IL‐4‐Dependent Effector Phase in Autoimmune Exocrinopathy as Defined by the NOD.IL‐4‐Gene Knockout Mouse Model of Sjögren's Syndrome

IL‐4‐Dependent Effector Phase in Autoimmune Exocrinopathy as Defined by the NOD.IL‐4‐Gene Knockout Mouse Model of Sjögren's Syndrome

Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system

Development of Sjögren’s Syndrome in Nonobese Diabetic-Derived Autoimmune-Prone C57BL/6.NOD-Aec1Aec2 Mice Is Dependent on Complement Component-3

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