Stock No.'s 008053, 008054, 008055, 008056, 008057, 008058, 008059 and 008060, are the result of crossing segments of C57L/J derived Chromosome 11 into the NOD/Bdc background. These strains experience significantly reduced diabetes and are useful for identifying candidate genes within the Idd4 subloci.
Marcia McDuffie, Univ. of Virginia Dept. of Medicine
|Marker Symbol||Marker Name|
|Idd4||insulin dependent diabetes susceptibility 4|
|D11Mit314||DNA Segment, Chr 11, Massachusetts Institute of Technology 314|
|D11Mit42||DNA segment, Chr 11, Massachusetts Institute of Technology 42|
This NOD congenic strain, commonly referred to as NOD.Lc11 or DR3, carries Chromosome 11 alleles, D11Mit314 (51Mb) through D11Mit42 (112Mb), derived from C57L/J including Idd4 and a candidate gene Csf2. Diabetes incidence in this diabetes resistant strain is reported to be 9% in the females and 0% in males compared to 70% in female and 40% in male NOD/Bdc control mice. NOD.Lc11 mice develop mild periductular infiltrates early in life and by 44 weeks of age histological analysis indicates healthy islet beta cells and normal amounts of stored insulin. Neonates injected with T cells from 8-week-old prediabetic NOD females and from old NOD mice were resistant to diabetes by 25 weeks of age. Splenic and lymph node derived T cells from NOD.Lc11 mice fail to cause diabetes or beta cell damage in NOD.scid neonatal mice, however 6 weeks post transfer the recipients develop severe invasive insulitis. Adult NOD.scid females that received T cells from NOD.Lc11 mice developed diabetes starting at 49 days post transfer (McDuffie, 2000; Semiromi et al 2007).
There appear to be several diabetes resistant regions (Idd4 ) on Chromosome 11, therefore this strain will be useful to positionally clone the Idd4 resistant loci.
This NOD congenic stock contains a large genomic segment from C57L/J introgressed into Chr 11. (C57L/J X NOD) F2 females homozygous for NOD derived H2g7, MHC class I K and MHC class II- I AB alleles were selected for backcrossing to NOD/Bdc. Breeders for further backcross to NOD/Bdc were selected based only on the dominant trait of lack of diabetes in females at 30 weeks of age. Diabetes resistant lines were analyzed using microsatellite markers. Microsatellite marker analysis identified one of the lines, DR4, with a large segment of C57L/J on Chr 7 (Stock No. 008061 NOD.L-(D7Mit253-D7Mit242)/McdfJ; while this line, DR3, (Stock No. 008053 NOD.L-(D11Mit314-D11Mit42)/McdfJ was identified with a large segment of C57L/J on Chr 11 (McDuffie, 2000). The C57L/J congenic interval retained in this stock includes Idd4 and candidate genes Csf2, Stat3, Stat5a and Stat5b alleles. In 2008, the Type 1 Diabetes Resource received this stock at N5F42.