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 1980
0 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
), 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 1991
0 1991). Develops Coombs'-positive
hemolytic autoimmune anaemia (Baxter and Mandel
). 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.
H. and Scarpellino L. (1991) Nonobese diabetic and nonobese nondiabetic
mice have unique MHC class II haplotypes. Immunogenet. 34,
A. G. and Mandel T. E. (1991) Hemolytic anemia in non-obese diabetic mice.
Eur. J. Immunol. 21, 2051-2055.
A. G. and Cooke A. (1993) Complement lytic activity has no role in the
pathogenesis of autoimmune diabetes in NOD mice. Diabetes 42,
and Maestroni G. J. M. (1996) Melatonin rhythms in mice and its role in
autoimmune diseases. Periodicum Biologorum 98, 451-457.
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.
H. and Makino S. (1992) The murine autoimmune diabetes model: NOD and
related strains. Adv. Immunol. 52, 285-322.
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,
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.
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
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.
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.
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.
INBRED STRAINS OF MICE
Updated 9 Apr. 1998
MRC Toxicology Unit, Hodgkin Building,
University of Leicester,