An NZW-Derived Interval on Chromosome 7 Moderates Sialadenitis, But Not Insulitis in Congenic Nonobese Diabetic Mice

Burt, Rachel; Watkins, Laura E.; Tan, Iris; Wang, Nancy; Quirk, Fiona; Mackin, Leanne; Morgan, Phillip O.; Zhang, Jianguo; Berzins, Stuart P.; Morahan, Grant; Brodnicki, Thomas C.

doi:10.4049/jimmunol.0903149

Cited by 7 publications

(4 citation statements)

References 64 publications

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“…Supporting the notion of a certain independence between degree of inflammation and glandular hypofunction, introduction of an NZW-derived interval of chromosome 7 (annotated Ssial3 ) into NOD mice moderated sialoadenitis without ameliorating salivary gland function [55]. Analyses of dozens of inflammatory mediators in serum and saliva obtained from NOD mice, furthermore, only revealed a minimal number of biomarkers correlating with several SS-related disease manifestations in an association network [56].…”

Section: Murine Models Of Spontaneous Diseasementioning

confidence: 99%

Sjögren's syndrome: studying the disease in mice

et al. 2011

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Sjögren's syndrome (SS), a systemic autoimmune disease, is characterized by inflammation of exocrine tissues accompanied by a significant loss of their secretory function. Clinical symptoms develop late and there are no diagnostic tests enabling early diagnosis of SS. Thus, particularly to study these covert stages, researchers turn to studying animal models where mice provide great freedom for genetic manipulation and testing the effect of experimental intervention. The present review summarizes current literature pertaining to both spontaneous and extrinsic-factor induced SS-like diseases in mouse models, discussing advantages and disadvantages related to the use of murine models in SS research.

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Section: Murine Models Of Spontaneous Diseasementioning

confidence: 99%

Sjögren's syndrome: studying the disease in mice

et al. 2011

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“…This, however, does not preclude a potential contribution of increased pDC levels in other autoimmune diseases. Indeed, sialadenitis is less severe in NOD.NZW-Chr7 mice (17), which correlates with low pDC proportion. Further investigation of the pathophysiological processes leading to the distinct autoimmune pathologies of insulitis and sialadenitis in NOD mice may better characterize the contribution of pDC to specific autoimmune diseases.…”

Section: Discussionmentioning

confidence: 94%

“…First, NOD.NZW-Chr7 mice present a low proportion of pDC relative to NOD mice, but both strains show a comparable incidence of autoimmune diabetes (17), demonstrating that elevated proportion of pDC is not necessary for autoimmune diabetes progression. Second, both NOR mice, which are highly genetically related to NOD mice (47)(48)(49), and 129Sv mice (4) exhibit a high proportion of pDC similar to NOD mice, yet do not develop insulitis or diabetes.…”

Section: Discussionmentioning

confidence: 97%

The Size of the Plasmacytoid Dendritic Cell Compartment Is a Multigenic Trait Dominated by a Locus on Mouse Chromosome 7

Pelletier

Guimont-Desrochers

Ashton

et al. 2012

The Journal of Immunology

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Plasmacytoid dendritic cells (pDC) compose one of the many distinct dendritic cell subsets. The primary function of pDC is to potently produce type 1 IFNs upon stimulation, which is highly relevant in antiviral responses. Consequently, the ability to manipulate the size of the pDC compartment in vivo may increase the capacity to clear viral infections. In an attempt to identify genetic loci affecting the size of the pDC compartment, defined by both the proportion and absolute number of pDC, we undertook an unbiased genetic approach. Linkage analysis using inbred mouse strains identified a locus on chromosome 7 (Pdcc1) significantly linked to both the proportion and the absolute number of pDC in the spleen. Moreover, loci on either chromosome 11 (Pdcc2) or 9 (Pdcc3) modified the effect of Pdcc1 on chromosome 7 for the proportion and absolute number of pDC, respectively. Further analysis using mice congenic for chromosome 7 confirmed Pdcc1, demonstrating that variation within this genetic interval can regulate the size of the pDC compartment. Finally, mixed bone marrow chimera experiments showed that both the proportion and the absolute number of pDC are regulated by cell-intrinsic hematopoietic factors. Our findings highlight the multigenic regulation of the size of the pDC compartment and will facilitate the identification of genes linked to this trait.

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“…In addition to autoimmune diabetes and thyroiditis (20,132), NOD mice can present with both autoimmune diabetes and SS (137)(138)(139)(140)(141)(142)(143). T1D and SS can also co-occur in humans, with up to 55% of PWT1D exhibit symptoms of SS, such as keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth) (144).…”

Section: Polyautoimmunity In Nod Micementioning

confidence: 99%

The NOD Mouse Beyond Autoimmune Diabetes

et al. 2022

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Autoimmune diabetes arises spontaneously in Non-Obese Diabetic (NOD) mice, and the pathophysiology of this disease shares many similarities with human type 1 diabetes. Since its generation in 1980, the NOD mouse, derived from the Cataract Shinogi strain, has represented the gold standard of spontaneous disease models, allowing to investigate autoimmune diabetes disease progression and susceptibility traits, as well as to test a wide array of potential treatments and therapies. Beyond autoimmune diabetes, NOD mice also exhibit polyautoimmunity, presenting with a low incidence of autoimmune thyroiditis and Sjögren’s syndrome. Genetic manipulation of the NOD strain has led to the generation of new mouse models facilitating the study of these and other autoimmune pathologies. For instance, following deletion of specific genes or via insertion of resistance alleles at genetic loci, NOD mice can become fully resistant to autoimmune diabetes; yet the newly generated diabetes-resistant NOD strains often show a high incidence of other autoimmune diseases. This suggests that the NOD genetic background is highly autoimmune-prone and that genetic manipulations can shift the autoimmune response from the pancreas to other organs. Overall, multiple NOD variant strains have become invaluable tools for understanding the pathophysiology of and for dissecting the genetic susceptibility of organ-specific autoimmune diseases. An interesting commonality to all autoimmune diseases developing in variant strains of the NOD mice is the presence of autoantibodies. This review will present the NOD mouse as a model for studying autoimmune diseases beyond autoimmune diabetes.

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An NZW-Derived Interval on Chromosome 7 Moderates Sialadenitis, But Not Insulitis in Congenic Nonobese Diabetic Mice

Cited by 7 publications

References 64 publications

Sjögren's syndrome: studying the disease in mice

Sjögren's syndrome: studying the disease in mice

The Size of the Plasmacytoid Dendritic Cell Compartment Is a Multigenic Trait Dominated by a Locus on Mouse Chromosome 7

The NOD Mouse Beyond Autoimmune Diabetes

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