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Inbred Strains of Mice: NOD


Inbr (Komeda) 22. Albino: c. Origin: A substrain developed by selection for diabetes (high fasting blood glucose) from F6 of the CTS strain, which was derived from outbred Jcl:ICR mice (Makino et al 19800 1980). At F13 a non-diabetic substrain now designated NON was separated from the main diabetic colony, though care should be taken in using this as a control strain (Leiter 1993), and at F20 a female was found with spontaneous insulin-dependent diabetes mellitus (IDDM). The origin and characteristics of this strain has been reviewed by Kikutani and Makino (1992) and Leiter (1993), and there is now an extensive literature on the characteristics of the strain. There is some evidence that substrains exist which differ in the incidence of IDDM even when maintained in a common environment (see Leiter 1993)


About 80% of females and 20% of males develop insulin-dependent diabetes by the age of 30 weeks, though this is dependent on environmentazl conditions. This is associated with insulitis, a leukocyte infiltration of the pancreas with a marked decrease in pancreatic insulin content by about 12 weeks of age in females. Genetic analysis suggests that the diabetes is dependent on multiple recessive loci including one associated with the H2, and another with the Thy1/Apoa1 loci (Prochazka et al 1989, Wicker et al 1989). Has a unique MHC class II haplotype (Acha-Orbea and Scarpellino 1991). Type I insulin-dependent diabetes is associated with overexpression of class I major histocompatibility complex proteins on pancreatic islet cells and is prevented by anti-interferon-gamma antibody (Kay et al 19910 1991). Develops Coombs'-positive hemolytic autoimmune anaemia (Baxter and Mandel 1991). Rare spontaneous myoepitheliomas arising from myoepithelial cells of various exocrine glands have been observed (Sundberg et al 1991). Defect in the expression of the alloantigen, Ly6C, which is not detectable on spleen or lymph node cells (c.f. NZB and ST but contrast most other strains) and may be due to an interruption in the flanking region of the Ly6C gene at a point 475 bp upstream of the transcription initiation site (Philbrick et al 1990). NOD mice may have abnormalities in IFN-gamma production. (Tsumura et al 1989). Newborn pinealectomy accelerates the development of diabetes in females while exogenous melatonin protects the mice though it results in an increase in insulin autoantibodies (Conti and Maestroni, 1996).

Low susceptibility to Mycobacterium leprae (contrast MRL-lpr) (Yogi et al 1989). Lymphoid cells are resistant to several signals known to induce apoptosis in other mouse strains, suggesting that they have a defect in mechanisms mediating programmed cell death (Leijon et al, 1994). Do not differ significantly from mice of other strains in antioxidant enzyme profiles, suggesting that it is unlikely that any adverse effect of oxygen radicals on beta cells is a result of antioxidant enzyme deficiency (Cornelius et al, 1993). Mice are C5-complement deficient (Hc0) (Baxter and Cooke, 1993).

Maint. by Jic, Wak.

Acha-Orbea H. and Scarpellino L. (1991) Nonobese diabetic and nonobese nondiabetic mice have unique MHC class II haplotypes. Immunogenet. 34, 57-59.

Baxter A. G. and Mandel T. E. (1991) Hemolytic anemia in non-obese diabetic mice. Eur. J. Immunol. 21, 2051-2055.

Baxter A. G. and Cooke A. (1993) Complement lytic activity has no role in the pathogenesis of autoimmune diabetes in NOD mice. Diabetes 42, 1574-1578.

Conti A. and Maestroni G. J. M. (1996) Melatonin rhythms in mice and its role in autoimmune diseases. Periodicum Biologorum 98, 451-457.

Cornelius J. G., Luttge B. G., and Peck A. B. (1993) Antioxidant enzyme activities in IDD-prone and IDD-resistant mice: A comparative study. Free Radical Biology and Medicine 14, 409-420.

Kay T. W. H., Campbell I. L., Oxbrow L., and Harrison L. C. (1991) Overexpression of class I major histocompatibility complex accompanies insulinitis in the non-obese diabetic mouse and is prevented by anti-interferon-gamma antibody. Diabetologia 34, 779-785.

Kikutani H. and Makino S. (1992) The murine autoimmune diabetes model: NOD and related strains. Adv. Immunol. 52, 285-322.

Leijon K., Hammarstrom B., and Holmberg D. (1994) Non-obese diabetic (NOD) mice display enhanced immune responses and prolonged survival of lymphoid cells. International Immunology 6, 339-345.

Leiter E.H. (1993) The NOD mouse: A model for analyzing the interplay between heredity and environment in development of autoimmune disease. ILAR News 35, 4-14.

Makino S., Kunimoto K., Muraoka Y., Mizushima Y., Katagiri K., and Tochino Y. (1980) Breeding of a non-obese, diabetic strain of mice. Exp. Animals (Japan) 29, 1-13.

Philbrick W. M., Maher S. E., Bridgett M. M., and Bothwell A. L. (1990) A recombination event in the 5' flanking region of the Ly-6C gene correlates with impaired expression in the NOD, NZB and ST strains of mice. EMBO Journal 9, 2485-2492.

Prochazka M., Serrez D. V., Worthen S. M., and Leiter E. H. (1989) Genetic control of diabetogenesis in NOD/Lt mice.# Development and analysis of congenic stocks. Diabetes 38, 14-46.

Tsumura H., Komada H., Ito Y., and Shimura K. (1989) In vitro and in vivo interferon production in NOD mice. Lab. Animal Sci. 39, 575-578.

Wicker L. S., Miller B. J., Fischer P. A., Pressey A., and Peterson L. B. (1989) Genetic control of diabetes and insulitis in the nonobese diabetic mouse. Pedigree analysis of a diabetic H-2nod/b heterozygote. J. Immunol. 142, 781-784.

Yogi Y., Nakamura K., and Suzuki A. (1989) The experimental inoculation with Mycobacterium leprae in autoimmune mice: results of MRL/lpr mice inoculated into the right hind foot. Japanese Journal of Leprosy 58, 235-240.

Updated 9 Apr. 1998
Michael FW Festing
MRC Toxicology Unit, Hodgkin Building,
University of Leicester, UK

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