NOD.NOR-(D2Mit490-Ada)/LtJ

Stock number: 002346
Product name: NOD.NOR-Idd13A
Research areas: Diabetes and Obesity Research

Description

These congenic mice carry the Il1b^NOR and Idd13^r alleles from the NOR/Lt inbred strain and show a reduced incidence of diabetes.

Detailed description

This NOD/Lt congenic strain is carrying alleles derived from strain NOR/Lt at the interleukin 1b (Il1b^NOR) and the insulin dependent diabetes susceptibility 13 (Idd13^r) loci. Incidence of diabetes among NOD.NOR-D2Mit490-Ada (Idd13^r, Il1b^NOR) females was 16% and 26% at 30 weeks and 52 weeks of age, respectively, compared with 100% diabetes incidence by 30 weeks in NOD/Lt females; no diabetes was observed in congenic males. Histologic examination of the pancreases of year-old non-diabetic congenic mice revealed extensive perivascular/periductal leukocytic infiltration; infiltrates associated with islets "were primarily peri-insular, with granulated beta cell mass largely preserved in >80% of the islets. This histopathology is similar to that observed in year-old NOR/Lt mice of both sexes. "Thus, Idd13^rdoes not mediate IDDM resistance in NOR mice by preventing lymphocyte infiltration of the pancreas, but by inhibiting "activation of autoimmune effector functions." This strain is useful for dissecting the role of non-MHC susceptibility genes in autoimmune diabetes.

Development

Mice of a congenic strain (at N12) carrying a defined segment of Chr 2 that included the IDDM resistant allele of NOR/Lt at the insulin dependent diabetes susceptibility locus Idd13 were further backcrossed to NOD/Lt. At backcross generation N21, the truncated NOR-derived segment of Chr 2 was fixed to homozygosity in each of three lines by sib mating. NOD.NOR-D2Mit490-Ada (Idd13^r , Il1b^NOR) carries a 31.5 cM interval of Chr 2 from NOR/Lt extending from D2Mit490 through Ada that "contains all markers previously found to be linked to Idd13 -mediated IDDM resistance in NOR mice." This region of Chr 2 in NOR was originally derived from the C57BL/6 contribution to strain C57BLKS/J; thus, this congenic strain carries the B6 alleles for the microsatellite markers and the functional genes (e.g., Zfp106^a/H3a^a, B2m^b , and presumably Il1b) in this region. (Serreze et al. refer to this strain as NOD.D2Mit490-Mit144^NOR .)

Allele

Symbol: Idd13^NOR/Lt
Name: NOR/Lt
MGI accession ID: MGI:3036816
Generation method: QTL
Marker symbol: Idd13
Marker name: insulin dependent diabetes susceptibility 13
Chromosome: 2
Strain of origin: NOR/Lt
Molecular note: This allele confers resistance to insulin dependent diabetes compared to NOD/Lt.

Allele

MGI accession ID: MGI:87916
Marker symbol: Ada
Marker name: adenosine deaminase
Chromosome: 2

Allele

MGI accession ID: MGI:105685
Marker symbol: D2Mit490
Marker name: DNA Segment, Chr 2 Massachusetts Institute of Technology 490
Chromosome: 2

Allele

MGI accession ID: MGI:96543
Marker symbol: Il1b
Marker name: interleukin 1 beta
Chromosome: 2