The NOD Mouse: A Model for Insulin‐Dependent Diabetes Mellitus

Leiter, Edward H.

doi:10.1002/0471142735.im1509s24

Cited by 107 publications

(108 citation statements)

References 50 publications

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“…Experimental design precluded developing a diabetes incidence curve for females in our NOD colony. The diabetes incidence for males was Ͼ50% at 30 weeks of age (n ϭ 8), consistent with published work (1).…”

Section: Methodssupporting

confidence: 90%

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Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

et al. 2007

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OBJECTIVE-Pregnant diabetic women are at a 4 -12 times higher risk for preeclampsia, an urgent acute-onset complication of mid-to late gestation, than normal pregnant women. Hallmarks of preeclampsia are hypertension, proteinuria, and incomplete modification of endometrial spiral arteries. Transient proangiogenic lymphocytes called uterine natural killer (uNK) cells are implicated in human and rodent spiral artery modification. We studied mid-to late gestations in spontaneously type 1 diabetic NOD mice to investigate whether diabetes alters uNK cell homing and/or function.RESEARCH DESIGN AND METHODS-Normoglycemic, prediabetic, and diabetic NOD mice and controls were mated. Lymphocytes and endometrial endothelium and decidua were studied histologically and in functional assays.RESULTS-Conception accelerated progression to overt diabetes in NOD females who had limited spiral artery development, heavier placentas, and lighter fetuses displaying numerous birth defects compared with controls. UNK cell numbers were reduced in the decidua basalis of diabetic females, whereas interferon-␥ production was elevated. In diabetic NOD mice, decidual expression of the mucosal vascular addressin cell adhesion molecule (MAdCAM)-1 was aberrant in position, whereas vascular cell adhesion molecule (VCAM)-1 expression was reduced. Assays of lymphocyte adhesion to tissue sections under shear forces indicated that diabetes compromises the potential homing functions of both endometrial endothelium and peripheral NK cells.CONCLUSIONS-In diabetes, gestational endometrium has immune and vascular defects that likely contribute to murine fetal loss and birth defects. Analogous problems and preeclampsia in diabetic women may involve similar mechanisms. Diabetes

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Section: Methodssupporting

confidence: 90%

“…These include death, birth defects, and potential for early development of type 1 diabetes in offspring (10 -12). Whereas normoglycemic NOD mice are excellent breeders (1), features of mid-gestation implantation sites in overtly diabetic mice are unknown.…”

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confidence: 99%

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

et al. 2007

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“…Subsequently, tissues were paraffin embedded and cut into 5 mm sections. Serial paraffin sections were stained by hematoxylin and eosin (H&E) coupled with aldehyde fuchsin as previously described (38). Images of islets were taken using a Zeiss Axioplan light microscope coupled with an AxioCam ICc3 color camera at 2003 or 6303 magnifications.…”

Section: Insulitis Scoring and Pancreatic Toluidine Blue Stainingmentioning

confidence: 99%

Type 1 Diabetes in NOD Mice Unaffected by Mast Cell Deficiency

Gutierrez

Schönefeldt

et al. 2014

Diabetes

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Mast cells have been invoked as important players in immune responses associated with autoimmune diseases. Based on in vitro studies, or in vivo through the use of Kit mutant mice, mast cells have been suggested to play immunological roles in direct antigen presentation to both CD4+ and CD8+ T cells, in the regulation of T-cell and dendritic cell migration to lymph nodes, and in Th1 versus Th2 polarization, all of which could significantly impact the immune response against self-antigens in autoimmune disease, including type 1 diabetes (T1D). Until now, the role of mast cells in the onset and incidence of T1D has only been indirectly tested through the use of low-specificity mast cell inhibitors and activators, and published studies reported contrasting results. Our three laboratories have generated independently two strains of mast cell–deficient nonobese diabetic (NOD) mice, NOD.Cpa3Cre/+ (Heidelberg) and NOD.KitW-sh/W-sh (Leuven and Boston), to address the effects of mast cell deficiency on the development of T1D in the NOD strain. Our collective data demonstrate that both incidence and progression of T1D in NOD mice are independent of mast cells. Moreover, analysis of pancreatic lymph node cells indicated that lack of mast cells has no discernible effect on the autoimmune response, which involves both innate and adaptive immune components. Our results demonstrate that mast cells are not involved in T1D in the NOD strain, making their role in this process nonessential and excluding them as potential therapeutic targets.

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“…Overtly diabetic NOD females are usually removed from breeding programs due to their fragile health and poor reproductive fitness [17]. However, with diligent supplemented husbandry and nursing care (see methods), diabetic dams in this study delivered live pups.…”

Section: Offspring Of Diabetic Nod Females Are Growth Compromisedmentioning

confidence: 99%

Circulatory and renal consequences of pregnancy in diabetic NOD mice

et al. 2011

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Objectives-Women with diabetes have elevated gestational risks for severe hemodynamic complications, including preeclampsia in mid-to late pregnancy. This study employed continuous, chronic radiotelemetry to compare the hemodynamic patterns in non-obese diabetic (NOD) mice who were overtly diabetic or normoglycemic throughout gestation. We hypothesized that overtly diabetic, pregnant NOD mice would develop gestational hypertension and provide understanding of mechanisms in progression of this pathology.Study Design-Telemeter-implanted, age-matched NOD females with and without diabetes were assessed for six hemodynamic parameters (mean, systolic, diastolic, pulse pressures, heart rate and activity) prior to mating, over pregnancy and over a 72 hr post-partum interval. Urinalysis, serum biochemistry and renal histopathology were also conducted.Results-Pregnant, normoglycemic NOD mice had a hemodynamic profile similar to other inbred strains, despite insulitis. This pattern was characterized by an interval of pre-implantation stability, post implantation decline in arterial pressure to mid gestation, and then a rebound to prepregnancy baseline during later gestation. Overtly diabetic NOD mice had a blood pressure profile that was normal until mid-gestation then become mildly hypotensive (−7mmHg, P<0.05), severely bradycardic (−80bpm, P<0.01) and showed signs of acute kidney injury. Pups born to diabetic dams were viable but growth restricted, despite their mothers' failing health, which did not rebound post-partum (−10% pre-pregnancy pressure and HR, P<0.05).Conclusions-Pregnancy accelerates circulatory and renal pathologies in overtly diabetic NOD mice and is characterized by depressed arterial pressure from mid-gestation and birth of growth 45 restricted offspring. KeywordsType 1 Diabetes Mellitus; Pregnancy; Radiotelemetry; Hemodynamics Correspondence: Anne Croy, Department of Biomedical and Molecular Sciences, Room 924 Botterell Hall, 18 Stuart Street, Queen's University, Kingston, Ontario, Canada K7L 3N6, Fax: 1-613-533-2022, Telephone: 1-613-533-2859 CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptCardiovascular complications are common and progressive in Type 1 Diabetes Mellitus (T1DM), often leading to significant morbidity and death. Pregnancy has been described as a physiological stressor and early predictor of cardiovascular disease when outcomes are abnormal [1]. Women with pre-existing diabetes (autoimmune and non-insulin-dependent diabetes mellitus) are considered high-risk obstetrical patients with significantly increased risks for complications; including worsening of pre-existing diabetic sequelae (diabetic nephropathy, retinopathy and altered glycemic control), pregnancy-induced hypertension, preeclampsia and thromboembolic events [2][3][4][5]. Severity of the pre-existing diabetic disease status rather than glycemic control is used to stratify risk for these women. Risks for the fetuses and children of mothers with diabetes include congenital defects, growth restricti...

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The NOD Mouse: A Model for Insulin‐Dependent Diabetes Mellitus

Cited by 107 publications

References 50 publications

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

Type 1 Diabetes in NOD Mice Unaffected by Mast Cell Deficiency

Circulatory and renal consequences of pregnancy in diabetic NOD mice

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