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. 2010 Nov;6(6):939-55.
doi: 10.1586/eci.10.68.

An update on the use of NOD mice to study autoimmune (Type 1) diabetes

Rodolfo José Chaparro  1 , Teresa P Dilorenzo
Affiliations

An update on the use of NOD mice to study autoimmune (Type 1) diabetes

Rodolfo José Chaparro et al. Expert Rev Clin Immunol. 2010 Nov.

Abstract

The widely used nonobese diabetic (NOD) mouse model of autoimmune (Type 1) diabetes mellitus shares multiple characteristics with the human disease, and studies employing this model continue to yield clinically relevant and important information. Here, we review some of the recent key findings obtained from NOD mouse investigations that have both advanced our understanding of disease pathogenesis and suggested new therapeutic targets and approaches. Areas discussed include antigen discovery, identification of genes and pathways contributing to disease susceptibility, development of strategies to image islet inflammation and the testing of therapeutics. We also review recent technical advances that, combined with an improved understanding of the NOD mouse model's limitations, should work to ensure its popularity, utility and relevance in the years ahead.

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Figures

Figure 1
Figure 1. The nonobese diabetic mouse model continues to be a mainstay of Type 1 diabetes research
The PubMed database was searched using the search string ‘NOD mice, diabetes.’ The plot depicts retrieved citations for each year, excluding review articles.
Figure 2
Figure 2. Recent contributions of the nonobese diabetic mouse model to our understanding of Type 1 diabetes have occurred in the indicated areas
Examples of discoveries covered within this review are shown. See text for details and references. G-CSF: Granulocyte colony-stimulating factor; GM-CSF: Granulocyte-macrophage colony-stimulating factor; NOD: Nonobese diabetic; PDX1: Pancreatic duodenal homeobox 1.
Figure 3
Figure 3. Islet-specific genes remain largely unexplored as Type 1 diabetes antigens
Islet specificity was calculated as the frequency of a given transcript within the Unigene mouse islets expressed sequence tag library 16013 [178] divided by the cumulative frequency of that transcript in all tissues represented by the Unigene ‘profiles’ dataset excluding whole pancreas [211,212]. The islet library contained 24,059 expressed sequence tags corresponding to 6451 unique genes. Gene bins are 0.1 islet specificity units wide. Known islet-specific Type 1 diabetes antigens are positioned along the smoothed distribution according to their islet specificity values. Approximately 700 genes span the region bounded by IA-2β at the left and INS at the right, suggesting a rich source of as-yet unidentified Type 1 diabetes antigens.
See this image and copyright information in PMC

References

    1. Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y. Breeding of a non-obese, diabetic strain of mice. Exp. Anim. 1980;29(1):1–13. - PubMed
    1. Shoda LK, Young DL, Ramanujan S, et al. A comprehensive review of interventions in the NOD mouse and implications for translation. Immunity. 2005;23(2):115–126. - PubMed
    1. Suri A, Walters JJ, Gross ML, Unanue ER. Natural peptides selected by diabetogenic DQ8 and murine I-Ag7 molecules show common sequence specificity. J. Clin. Invest. 2005;115(8):2268–2276. - PMC - PubMed
    1. Wang J, Wicker LS, Santamaria P. IL-2 and its high-affinity receptor: genetic control of immunoregulation and autoimmunity. Semin. Immunol. 2009;21(6):363–371. - PubMed
    1. Lieberman SM, Evans AM, Han B, et al. Identification of the β cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes. Proc. Natl Acad. Sci. USA. 2003;100(14):8384–8388. - PMC - PubMed
Websites
    1. NCT00837759: Novel therapy combining regenerative stimuli and immunomodulation to preserve β-cell function in new onset Type 1 diabetes. http://clinicaltrials.gov/ct2/show/NCT00837759.
    1. NCT00873925: Cord blood plus vitamin D and omega 3s in T1D. http://clinicaltrials.gov/ct2/show/NCT00873925.
    1. NCT01068951: Treatment of patients with new onset of Type 1 diabetes with mesenchymal stem cells. http://clinicaltrials.gov/ct2/show/NCT01068951.
    1. NCT00378508: Anti-CD3 mAb treatment of recent onset Type 1 diabetes. http://clinicaltrials.gov/ct2/show/NCT00378508.
    1. NCT00678886: Trial of otelixizumab for adults with newly diagnosed Type 1 diabetes mellitus (autoimmune): DEFEND-1. http://clinicaltrials.gov/ct2/show/NCT00678886.

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