Diabetes, Vol 38, Issue 10 1296-1300, Copyright © 1989 by American Diabetes Association
Comparison of high- and low-diabetes-incidence NOD mouse strains
AG Baxter, MA Adams and TE Mandel
Walter & Eliza Hall Institute, Royal Melbourne Hospital, Parkville, Victoria, Australia.
The nonobese diabetic (NOD) mouse is a model of insulin-dependent diabetes
mellitus. These mice develop insulinopenia and hyperglycemia secondary to
beta-cell destruction, which is associated with insulitis and autoantibody
production. We have two strains of NOD mice: a low-incidence strain
(NOD/Wehi), in which less than 10% females and less than 1% males develop
diabetes by 150 days despite intense insulitis, and a high-incidence strain
(NOD/Lt), in which most females and many males develop diabetes by 150
days. This phenotypic difference has been maintained for 24 mo despite
identical housing in our specific pathogen-free unit. Reciprocal skin
grafting and allozyme electrophoresis have not identified a difference
between the strains. Mixed-lymphocyte cultures were performed with splenic
T-lymphocytes cultured with equal numbers of irradiated stimulator
splenocytes for 3-6 days. NOD/Wehi mice demonstrated a heightened syngeneic
mixed-lymphocyte response (SMLR), averaging 19% of the allogeneic response
to CBA/CaHWehi cells. The response to NOD/Lt stimulator cells was not
significantly different from the syngeneic response. In contrast, NOD/Lt
mice had an SMLR similar to that of BALB/cAnBradleyWehi control mice,
averaging 5% of the allogeneic response. NOD/Lt cells also responded
similarly to NOD/Wehi stimulator cells and briskly to allogeneic cells. The
heightened SMLR in NOD/Wehi mice may reflect active generation of
suppressor function, and this may account for the low incidence of
diabetes.