|Allele Type||Gene Symbol||Gene Name|
|QTL||Idd4||insulin dependent diabetes susceptibility 4|
|Marker Symbol||Marker Name|
|D1Mit18||DNA segment, Chr 1, Massachusetts Institute of Technology 18|
|D11Mit325||DNA Segment, Chr 11, Massachusetts Institute of Technology 325|
|D11Mit41||DNA segment, Chr 11, Massachusetts Institute of Technology 41|
Genetic Quality Control of this Chromosome 11, Idd4 congenic stock indicates Chromosome 1 markers in the Idd5 region are of C57BL/6 origin.
The donating investigator reports diabetes onset of female NOD.B6-(D11Mit38-D11Mit325)/DelJ (commonly called NOD.B6-Idd4B, Chromosome 11, 49cM) is delayed, with 40% of the females 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-Idd4B mice indicates 70% of the islets are normal compared with 50% in NOD controls. At 25-30 weeks of age, 45% of NOD.B6-Idd4B islets are infiltrated compared to 80% in NOD controls. Immunohistochemical assays indicate normal amounts of stored insulin. Purified splenic T-cells from 12-week-old, non-diabetic NOD.B6-Idd4B females alone are able to induce diabetes in NOD.Prkdcscid female recipients. Diabetes onset is delayed in recipients of NOD.B6-Idd4B T-cells only, with about 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-Idd4B T-cells. TCR stimulated T-cell proliferative responses or anti-CD3 stimulated splenic T-cells express more CD69, CD25, and produce more IL2, IL4 and interferon gamma than NOD controls (Grattan et al. 2002).
Surprisingly, Genetic Quality Control completed at the Jackson Laboratory indicates Chromosome 1 markers in the Idd5 region are of C57BL/6 origin and may be viewed at QC of Idd4 congenic stocks. The reported conclusion of diabetes resistance will be re-evaluated in light of the additional genetic quality control results once the B6 contaminating genome on Chromosome 1 has been eliminated.
This strain may be useful for identifying genes involved with diabetes resistance located within the Idd4 region of Chromosome 11.
The three Idd4 subloci mape to Chr 11. Chr 11 genomic segments from C57BL/6 were transferred to NOD by outcross to an NODxC57BL/6J F2 mouse followed by 3 backcross cycles to NOD/Del with selection for B6 markers on Chr. 11 prior to inbreeding. T.L.Delovitch established three congenic strains based on their congenic intervals, D11Nds1-D11Mit325 (43.8-49cM), D11Mit38-D11Mit325 (49cM) and D11Mit38 (49cM). The 5.2cM region located between D11Nds1 - D11Mit325 of Chr. 11 is known to contain Nos2 (45.6cM) Mpmv4 (48cM), Xmv42 (53cM), Mpo, (49cM, D11Mit38) and the beta-chemokine gene family, including, Ccl1 (Tcr3, 47cM), Ccl2(Mcp1, 46.5cM), Ccl3 (Mip1a, 47.59cM), Ccl4 (Mip1b, 47.6cM) (Gill et al, 1995 and Grattan et al, 2002). Additional microsatellite analysis confirm all currently known Idd's are NOD in origin. (Grattan, et al., 2002). In 2005, The Jackson Laboratory received NOD.B6-(D11Mit38-D11Mit325)/DelJ (NOD.Idd4B) at generation N3F19.
Genetic quality control completed at The Jackson Laboratory indicates the following Chromosome 11 markers are of B6 origin: D11Mit325 (49cM), D11Mit38 (49cM) and D11Mit41 (49cM), while D11Mit339 (31.7cM), D11Nds1 (43.8cM), D11Mit245 (44.8cM) and D11Mit358 (52.5cM) are of NOD origin. Surprisingly, Chromosome 1 markers (Idd5 region) of B6 origin include: D1Mit18 (29.7cM), D1Mit180 (41cM), D1Jmp12 (47-51.4cM) and D1Mit445 (70cM), while D1Mit411 (18.5cM), D1Jmp23 (54.6cM), D1Mit26 (62.1cM) and D1Mit143 (86.6cM) are of NOD origin.