Utilization of the Non-Obese Diabetic (NOD) Mouse as an Animal Model for the Study of Secondary Sjögren’s Syndrome

Humphreys‐Beher, Michael G.; Hu, Yifei; Nakagawa, Yoichi; Wang, P L; Purushotham, Karnam R.

doi:10.1007/978-1-4615-2417-5_105

Cited by 117 publications

(96 citation statements)

References 9 publications

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“…These studies illustrate the capability of epithelial cells of the salivary glands to express cytokines that may attract DC. Such enhanced chemokine-cytokine expression might be linked to a metabolic abnormality or disturbed proliferation of the salivary gland epithelial cells of the NOD mouse; note that changes in the salivary protein composition in aging NOD mice have been observed (Humphreys-Beher, 1996;Humphreys-Beher et al, 1994). Early metabolic and/or growth abnormalities that precede the DC influx have also been noted in the thyroid gland of the biobreeding diabetes-prone rat, in which autoimmune thyroiditis develops after the influx of DC (Simons et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…In both mouse strains, perivascular and periductal lymphocytic infiltrates in the salivary and lacrimal glands are histologic hallmarks of the disease. In NOD mice (but not in MRL/lpr mice) the development of focal lymphocytic infiltrates in the salivary glands (sialoadenitis) is accompanied by a corresponding loss of the secretory function and changes in the protein composition of the saliva (Humphreys-Beher, 1996;Humphreys-Beher et al, 1994). These changes in protein composition have also been observed in NOD-SCID (severe combined immunodeficiency) mice (Robinson et al, 1996).…”

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confidence: 99%

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Two Different Types of Sialoadenitis in the NOD- and MRL/lpr Mouse Models for Sjögren's Syndrome: A Differential Role for Dendritic Cells in the Initiation of Sialoadenitis?

Blokland

Helden-Meeuwsen

Wierenga‐Wolf

et al. 2000

Laboratory Investigation

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SUMMARY: Sjö gren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal glands. In these glands, focal lymphocytic infiltrates develop. Little is known about the initiation of this autoimmune disease. Antigen-presenting cells (APC) such as dendritic cells (DC) can play a role in the initiation of autoimmunity. To date, no data on the presence of DC in Sjö gren's syndrome are available. Several mouse strains, the nonobese diabetic (NOD) and the MRL/lpr mouse, can be used as models for Sjö gren's syndrome. We compared the development of sialoadenitis in the submandibular glands (SMG) of NOD and MRL/lpr mice with particular focus on the presence of APC. DC, macrophages, T cells, and B cells in the SMG were studied by means of immunohistochemistry, after which positively stained cells were quantified. NOD-severe combined immunodeficiency (SCID) mice were used to study the presence of APC in the SMG in the absence of lymphocytes. Before lymphocytic infiltration, increased numbers of DC were detected in the SMG of NOD mice compared with those numbers in control mice and MRL/lpr mice, which suggests that DC play a role in the initiation of sialoadenitis in NOD mice. In the SMG of NOD mice, lymphocytic infiltrates organized in time. In MRL/lpr mice, however, lymphocytic infiltrates were already organized at the time of appearance. This organization was lost over time. In conclusion, two types of sialoadenitis are described in two mouse models for Sjö gren's syndrome. Differences exist with regard to early events that may lead to the development of sialoadenitis and to the composition and organization of inflammatory infiltrates. It is possible that different types of sialoadenitis also exist in humans and that the pathogenetic process in both the early and late phases of the autoimmune reaction differs among patients. (Lab Invest 2000, 80:575-585).

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Two Different Types of Sialoadenitis in the NOD- and MRL/lpr Mouse Models for Sjögren's Syndrome: A Differential Role for Dendritic Cells in the Initiation of Sialoadenitis?

Blokland

Helden-Meeuwsen

Wierenga‐Wolf

et al. 2000

Laboratory Investigation

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“…Mice in the Department of Pathology Mouse Colony become overtly diabetic starting at 12 Ϯ 2 weeks of age. For the current experiments, mice 10 -12 weeks of age were used to minimize xerostomic conditions related to the development of Sjö gren's syndrome-like exocrine tissue pathology, which does not develop before 12-16 weeks of age (31,32). Diabetic mice were maintained on daily intramuscular insulin injections (1 unit of Humulin/animal/24 h; Novo Nodisk, Bagsvaerd, Denmark) for 2 weeks before the initiation of the wound-healing experiments.…”

Section: Methodsmentioning

confidence: 99%

Reduced Oral Wound Healing in the NOD Mouse Model for Type 1 Autoimmune Diabetes and Its Reversal by Epidermal Growth Factor Supplementation

Nagy

Nagashima²,

Cha³

et al. 2001

Diabetes

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Using the NOD mouse, a model for type 1 diabetes, we examined how reduced concentrations of epidermal growth factor (EGF) in the saliva, after onset of type 1 diabetes, affect oral wound healing. Diabetic NOD/LtJ mice on insulin therapy, prediabetic NOD/LtJ, and ageand sex-matched BALB/cJ mice were given a cutaneous tongue punch and allowed to undergo normal healing. With diabetes onset and a reduction in saliva-derived growth factor levels, the rate of tongue wound healing was reduced compared with nondiabetic NOD/LtJ and healthy BALB/cJ mice. Addition of exogenous EGF to the drinking water did not accelerate the rate of healing in BALB/cJ or prediabetic NOD/LtJ; however, diabetic NOD/LtJ mice exhibited accelerated wound healing similar to healthy mice. These results demonstrate that loss of growth factors from saliva is associated with profoundly reduced oral wound healing, suggesting that therapeutic treatment with topical delivery may be beneficial to patients with type 1 diabetes and oral wound complications.

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“…We have recently shown that, before the development of lymphocytic infiltrates, DC accumulate in the submandibular glands of nonobese diabetic (NOD) mice, a mouse model for Sjögren's syndrome (Humphreys-Beher, 1996;Humphreys-Beher et al, 1994). In the MRL/lpr mouse, another mouse model for Sjögren's syndrome (Hoffman et al, 1984), hardly any DC were present before the onset of sialoadenitis (van Blokland et al, 2000).…”

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confidence: 99%

Professional Antigen Presenting Cells in Minor Salivary Glands in Sjögren's Syndrome: Potential Contribution to the Histopathological Diagnosis?

Blokland

Wierenga‐Wolf

Helden-Meeuwsen

et al. 2000

Laboratory Investigation

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SUMMARY:Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the salivary and lacrimal glands. We have shown that dendritic cells (DC) infiltrate the submandibular gland of the nonobese diabetic (NOD) mouse, a mouse model for Sjögren's syndrome, before lymphocytic infiltration, suggesting that these antigen-presenting cells (APC) may play a role in the initiation of Sjögren's syndrome. In later stages, DC and macrophages also form an important part of the infiltrate of the NOD sialoadenitis. To find out if DC and macrophages form part of the infiltrate in Sjögren's syndrome as well, and to determine whether they may be useful in the histopathological diagnosis of Sjögren's syndrome, we studied their presence in minor salivary glands (MSG) of patients with Sjögren's syndrome and patients with focal lymphocytic sialoadenitis (FLS), but without clinical or serological criteria of Sjögren's syndrome. Immunohistochemistry was applied, followed by semiquantitative analysis. DC and macrophages were present in all MSG; however, there were clear differences in marker expression between Sjögren's syndrome and FLS, on the one hand, and control tissue, on the other hand. CD1a ϩ DC and RFD9 ϩ macrophages were mainly observed in MSG in which a focal lymphocytic infiltrate was present. In fact, the diffuse presence of single CD1a ϩ DC and RFD9 ϩ macrophages correlated closely with the presence of a focal lymphocytic infiltrate in the MSG. This indicates that these cells could be of help during the evaluation of a MSG. Because the detection of APC is technically less cumbersome than a focal score, this parameter may perhaps replace the focal score in the histopathological diagnosis of Sjögren's syndrome. This study therefore prompts further investigation focusing on the presence of CD1a ϩ and RFD9 ϩ cells in the MSG of a large cohort of patients. (Lab Invest 2000, 80:1935-1941.

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Utilization of the Non-Obese Diabetic (NOD) Mouse as an Animal Model for the Study of Secondary Sjögren’s Syndrome

Cited by 117 publications

References 9 publications

Two Different Types of Sialoadenitis in the NOD- and MRL/lpr Mouse Models for Sjögren's Syndrome: A Differential Role for Dendritic Cells in the Initiation of Sialoadenitis?

Two Different Types of Sialoadenitis in the NOD- and MRL/lpr Mouse Models for Sjögren's Syndrome: A Differential Role for Dendritic Cells in the Initiation of Sialoadenitis?

Reduced Oral Wound Healing in the NOD Mouse Model for Type 1 Autoimmune Diabetes and Its Reversal by Epidermal Growth Factor Supplementation

Professional Antigen Presenting Cells in Minor Salivary Glands in Sjögren's Syndrome: Potential Contribution to the Histopathological Diagnosis?

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