The donating investigator reports diabetes onset of female NOD.B6-(D1Mit18-D1Mit445) (D11Nds1-D11Mit41)/DelJ (commonly called NOD.B6-Idd4A, Chromosome 11, 43.8-49cM) is delayed, with 15% of the females and 5% of the males becoming diabetic by 30 weeks of age. In the same colony, diabetes rates in NOD controls are 75% in females and 45% in males by 30 weeks of age. Histological examination of 12-week-old NOD.B6-Idd4A mice indicates 70% of the islets are normal compared with 50% in NOD controls. At 25-30 weeks of age, 10% of NOD.B6-Idd4A islets are infiltrated compared to 80% in NOD controls. Until 25-30 weeks of age, NOD.B6-Idd4A mice only develop periductal infiltrates with mild non-destructive insulitis. Additionally, immunohistochemical assays indicate normal amounts of stored insulin. Purified splenic T-cells from 12-week-old, non-diabetic NOD.B6-Idd4A females alone are able to induce diabetes in NOD.Prkdc^scid female recipients. Diabetes onset is slightly delayed in recipients of NOD.B6-Idd4A T-cells only, with 50% becoming diabetic by 70 days post transfer compared to 80% diabetic in recipients receiving either diabetic NOD T-cells alone or recipients co-transferred with diabetic NOD/ non-diabetic NOD.B6-Idd4A T-cells.TCR stimulated T-cell proliferative responses or anti-CD3 stimulated splenic T-cells express CD69, CD25, and produce IL2 at similar levels to NOD controls, while producing more IL4 and less interferon gamma than NOD controls (Grattan et al. 2002). 005311 incidence study and fine mapping data.

The reported conclusion of diabetes resistance has been re-evaluated since the C57BL/6 contaminating genome on Chromosome 1 has been eliminated in Stock No. 006809. Diabetes incidence studies performed at The Jackson Laboratory show an accelerated onset and incidence of diabetes in Stock No. 006809 females when compared with NOD/ShiLtJ controls and the original Stock No. 005311, while the diabetes onset and incidence in males is accelerated compared to the original Stock No. 005311 and is slightly less compared to NOD/ShiLtJ controls. 006809 incidence study and fine mapping data.