B6.NOD-(D3Mit132-Tshb)/J

Stock number: 003059
Product name: B6.NOD Idd3, 17/10/18
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

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).

Detailed description

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.

Development

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.

Allele

Symbol: Idd3^NOD
Name: NOD
MGI accession ID: MGI:2389018
Generation method: QTL
Marker symbol: Idd3
Marker name: insulin dependent diabetes susceptibility 3
Marker synonyms: Idd-3
Chromosome: 3
Strain of origin: NOD
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.
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.

Allele

Symbol: Idd10^NOD/ShiLt
Name: NOD/ShiLt
MGI accession ID: MGI:3036798
Generation method: QTL
Marker symbol: Idd10
Marker name: insulin dependent diabetes susceptibility 10
Marker synonyms: Idd-10
Chromosome: 3
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.

Allele

MGI accession ID: MGI:92400
Marker symbol: D3Mit132
Marker name: DNA segment, Chr 3, Massachusetts Institute of Technology 132
Chromosome: 3

Allele

MGI accession ID: MGI:98848
Marker symbol: Tshb
Marker name: thyroid stimulating hormone, beta subunit
Marker synonyms: thyrotropin; TSH-B; TSH-BETA
Chromosome: 3