Mice of this strain display resistance to diabetes.
Terry Delovitch, John P, Robarts Research Institute
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
QTL | Idd4 | insulin dependent diabetes susceptibility 4 |
Marker Symbol | Marker Name | |
---|---|---|
D1Mit445 | DNA Segment, Chr 1, Massachusetts Institute of Technology 445 | |
D11Nds1 | DNA segment, Chr 11, Nuffield Department of Surgery 1 | |
D1Mit18 | DNA segment, Chr 1, Massachusetts Institute of Technology 18 | |
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-(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.Prkdcscid 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.
The three Idd4 subloci map 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 other known Idd's are NOD in origin (Grattan, et al., 2002). In 2005, The Jackson Laboratory received NOD.B6-(D11Nds1-D11Mit325)/DelJ (NOD.Idd4A) at generation N3F18.
Genetic Quality Control data completed at the Jackson Laboratory indicates the following Chromosome 11 markers are of B6 origin: D11Nds1 (43.8cM), D11Mit245 (44.8cM), D11Mit325 (49cM), D11Mit38 (49cM) and D11Mit41 (49cM), while D11Mit339 (31.7cM) and D11Mit358 (52.5cM) are of NOD origin. Surprisingly, Chromosome 1 markers (Idd5 region) of C57BL/6 origin include: D1Mit18 (29.7cM), D1Mit180 (41cM), D1Jmp12 (47-51.4cM), D1Jmp23 (54.6cM) and D1Mit445 (70cM), while D1Mit411 (18.5cM), D1Mit143 (86.6cM) and D1Mit26 (62.1cM) are of NOD origin.
Allele Name | C57BL/6 |
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Allele Type | QTL |
Allele Synonym(s) | |
Gene Symbol and Name | Idd4, insulin dependent diabetes susceptibility 4 |
Gene Synonym(s) | |
Strain of Origin | C57BL/6 |
Chromosome | 11 |
Molecular Note | This allele confers increased T-cell proliferation compared to DBA/2 and NOD. |
Marker Synonym(s) | |
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Chromosome(s) | 1 |
Marker Synonym(s) | |
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Chromosome(s) | 11 |
Marker Synonym(s) | |
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Chromosome(s) | 1 |
Marker Synonym(s) | |
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Chromosome(s) | 11 |
When using the NOD.Idd4A mouse strain in a publication, please cite the originating article(s) and include JAX stock #005311 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous, 1 pair minimum |
Frozen Mouse Embryo | NOD.B6-(D1Mit18-D1Mit445)(D11Nds1-D11Mit41)/DelJ Frozen Embr | $2595.00 |
Frozen Mouse Embryo | NOD.B6-(D1Mit18-D1Mit445)(D11Nds1-D11Mit41)/DelJ Frozen Embr | $2595.00 |
Frozen Mouse Embryo | NOD.B6-(D1Mit18-D1Mit445)(D11Nds1-D11Mit41)/DelJ Frozen Embr | $3373.50 |
Frozen Mouse Embryo | NOD.B6-(D1Mit18-D1Mit445)(D11Nds1-D11Mit41)/DelJ Frozen Embr | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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