NOD/LtJ Mice Available
JAX® NOTES Issue 452, Winter 1993
Edward H. Leiter, Senior Staff Scientist
First Report
Nonobese diabetic (NOD) mice exhibit a susceptibility to spontaneous development of autoimmune (type 1) insulin dependent diabetes mellitus (IDDM). The mice were first reported in 1980. Since that time the strain has been widely established around the world and used by investigators to test compounds or devices to either prevent development of diabetes or to provide therapy.
The NOD and related strains were developed at Shionogi Research Laboratories in Aburahi, Japan (Makino et al, 1985; Makino et al, 1980). The NOD/LtJ mice in the Production Colonies of The Jackson Laboratory were derived from a breeding colony in Kyoto, Japan held be Dr. M. Hattori. The strain was brought to the United States in 1984.
Characteristics
Diabetes development in NOD mice is characterized by insulitis, a leukocytic infiltrate of the pancreatic islets. Marked decreases in pancreatic insulin content occur in females at about 12 weeks of age Gaskins et al., 1992a) and several weeks later in males. Onset of diabetes is marked by moderate glycosuria (1+ reading on Lilly Tes-TapeTM) and be a non-fasting plasma glucose higher than 250mg/dl. It is best to begin monitoring for development of glycosuria at weekly intervals starting at 10 weeks of age.
Susceptibility
Susceptibility to IDDM in NOD mice is polygenic and environment exerts a strong effect on gene penetrances. The major component of susceptibility, however, ins the unique MHC haplotype (H-2g7 Chr 17). Environment including housing conditions, health status, and diet all effect development of diabetes in the mice. It is suggested the literature be reviewed to understand the importance of environment before investigations using NOD mice are initiated.
Environment Important
Relating to environmental factors influencing diabetes susceptibility, genetic divergence of NOD substrains also has effected susceptibility. As work using various NOD substrains is compared, it appears that genetic divergence may account for some of the intra-colony differences in the incidence of diabetes in NOD male mice. For this reason, the Bibliography given at the end of this article includes only citations for the NOD/Lt strain maintained by Dr. Edward Leiter of The Jackson Laboratory. Incidence of diabetes in NOD/Lt females and males is currently at 85% and 37% respectively at 30 weeks of age.
NOD/LtJ mice are available from the Production Colonies of The Jackson Laboratory. Requests for the mice can be made by contacting the Customer Service Department at 1-800-422-MICE.
References
Gaskins, H.M. Prochazka, K. Hamaguchi, D. Serreze and E. Leiter. 1992a. Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes susceptible NOD/Lt from resistant NON/Lt mice. J. Clin. Invest. in press:
Makino, S., Y. Hayashi, Y. Muraoka and Y. Tochino. 1985. Establishment of the nonobese diabetic (NOD) mouse. In Current Topics in Clinical and Experimental Aspects of Diabetes Mellitus. N. Sakamoto, H. K. Min and S. Baba. Elsevier, Amsterdam. 25-32.
Makino, S., K. Kunimoto, Y. Muraoka, Y. Mizushima, K. Katagiri and Y. Tochino, 1980. Breeding of a non-obese, diabetic strain of mice. Exp. Anim. 29:1-8.
