NOD.B6-(D1Mit180-D1Mit143)(D11Mit38-D11Mit41)/DelJ

Stock number: 005313
Product name: NOD.Idd4C
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

Mice of this strain display resistance to diabetes.

Detailed description

The donating investigator reports diabetes onset of female NOD.B6-(D11Mit38-D11Mit41)/DelJ (commonly called NOD.B6-Idd4C, Chromosome 11, 49cM) is delayed, with 20% 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-Idd4C mice indicates 70% of the islets are normal compared with 50% in NOD controls. At 25-30 weeks of age, 45% of NOD.B6-Idd4C 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-Idd4C females alone are able to induce diabetes in NOD.Prkdc^scid female recipients. Diabetes onset is delayed in recipients of NOD.B6-Idd4C T-cells only, with about 40% 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-Idd4C T-cells. TCR stimulated T-cell proliferative responses or anti-CD3 stimulated splenic T-cells express more CD69, CD25, and produce more IL2, IL4 while producing equivalent amounts of interferon gamma as 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.

Development

The three Idd4 sub-loci have been mapped 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)/DelJ (NOD.Idd4C) at generation N3F19.

Genetic Quality Control completed at the Jackson Laboratory indicates the following Chromosome 11 markers are of B6 origin: D11Mit38 (49cM) and D11mit41 (49cM), while D11Mit325 (31.7cM) and D11Mit358 (52.5cM) are of NOD origin. Surprisingly, Chromosome 1 markers (Idd5 region) of B6 origin include: D1Mit180 (41cM), D1Jmp12 (47-51.4cM), D1Jmp23 (54.6cM), D1Mit445 (70cM), and D1Mit143 (86.6cM); while D1Mit18 (27 cM) and D1Mit26 (62.1cM) and D1Mit36 are of NOD origin.

Allele

Symbol: Idd4^C57BL/6
Name: C57BL/6
MGI accession ID: MGI:3036666
Generation method: QTL
Marker symbol: Idd4
Marker name: insulin dependent diabetes susceptibility 4
Chromosome: 11
Strain of origin: C57BL/6
Molecular note: This allele confers increased T-cell proliferation compared to DBA/2 and NOD.

Allele

MGI accession ID: MGI:91516
Marker symbol: D1Mit143
Marker name: DNA segment, Chr 1, Massachusetts Institute of Technology 143
Chromosome: 1

Allele

MGI accession ID: MGI:91557
Marker symbol: D1Mit180
Marker name: DNA segment, Chr 1, Massachusetts Institute of Technology 180
Chromosome: 1

Allele

MGI accession ID: MGI:89125
Marker symbol: D11Mit41
Marker name: DNA segment, Chr 11, Massachusetts Institute of Technology 41
Chromosome: 11

Allele

MGI accession ID: MGI:89121
Marker symbol: D11Mit38
Marker name: DNA segment, Chr 11, Massachusetts Institute of Technology 38
Chromosome: 11