These congenic mice carry a chromosomal segment from Chromosome 3 bound by an Mit marker and thyroid stimulating hormone, beta subunit (Tshb), and includes the insulin dependent diabetes susceptibility loci 3, 10, 17, and 18 (Idd3, Idd10, Idd17, Idd18).
|Allele Type||Gene Symbol||Gene Name|
|QTL||Idd3||insulin dependent diabetes susceptibility 3|
|Allele Type||Gene Symbol||Gene Name|
|QTL||Idd10||insulin dependent diabetes susceptibility 10|
|Marker Symbol||Marker Name|
|D3Mit132||DNA segment, Chr 3, Massachusetts Institute of Technology 132|
|Tshb||thyroid stimulating hormone, beta subunit|
This strain is congenic for a 43 cM segment of chromosome 3 extending from D3Mit132 through Tshb (thyroid stimulating hormone, beta subunit) that includes the diabetes susceptibility loci Idd3and Idd10 (which has been subsequently refined into three diabetes susceptibility loci: Idd10, Idd17, and Idd18). The name given this segment in the primary reference is c3. Upon histologic examination of the pancreas, B6.NOD-(D3Mit132-Tshb) female mice exhibited somewhat higher incidence of periinsulitis (perivascular, periductal and/or periislet infiltration by mononuclear cells) than did C57BL/6J controls, but the difference was not statistically significant. Female B6.NOD-(D3Mit132-Tshb) mice had twice the incidence of periinsulitis as males; female NOD mice are more susceptible than males to both insulitis and diabetes.
Genomic segments found in earlier linkage studies to include diabetogenic loci were transferred in the laboratory of E.K. Wakeland from NOD/Uf to C57BL/6 by six successive backcrosses (to N7). Sibs of each lineage were then intercrossed to generate mice homozygous for each segment. Microsatellite analysis was used to type mice for loci in the regions of interest. B6.NOD-(D3Mit132-Tshb) includes NOD alleles for both Chr 3 loci associated with insulitis and diabetes: Idd3,mapping near Il2;and Idd10,mapping near Tshb.
|Gene Symbol and Name||Idd3, insulin dependent diabetes susceptibility 3|
|Strain of Origin||NOD|
|General Note||Idd3 is also associated with insulitis. |
This allele (on a C57BL/6 background) also confers defective cytokine response (IL-2, IL-4, IFN-gamma, CSF-2) when stimulated with antigens (J:85823).
Il2 is a proposed candidate gene for Idd3. The electrophoretic mobility pattern of IL-2 correlates with type 1 diabetes incidence. Resistant strain C57BL/6J displays a heterogeneous IL-2 mobility pattern with major protein species ranging from 17-19 kDa while susceptible strains 129 and NOD display a homogeneous IL-2 mobility pattern with one major protein species at approximately 21-22 kDa.
|Molecular Note||This allele confers susceptibility to insulin dependent diabetes compared to C57BL/10. This allele confers decreased Ctla4 expression in activated T-cells compared to C57BL/6.|
|Gene Symbol and Name||Idd10, insulin dependent diabetes susceptibility 10|
|Strain of Origin||NOD/ShiLt|
|Molecular Note||This allele, in conjunction with NOD-derived alleles at Idd3 on a C57BL/6 background, confers defective cytokine response (IL-2, IL-4, IFN-gamma, CSF-2) when stimulated with antigens.|
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