NOD.B6(PL)-Idd3^C57BL/6/MrkTacJ

Stock number: 007934
Strain synonyms: NOD.B6-Idd3
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

The five strains that comprise this NOD congenic set (Stock No.'s 007930, 007931, 007932, 007933, 007934) contain the Idd3 region from non-NOD strains. All of these strains are viable and fertile. Stocks containing the Idd3 region from SWR/J, A/J, or CAST/EiJ are diabetes susceptible, while the congenic stocks containing the Idd3 region derived from C57BL/6 or CZECHI/EiJ are diabetes resistant and produce more IL2 mRNA than the diabetes susceptible strains. These strains have been used to positionally clone Idd3 on Chromosome 3 and continue to be valued to study the biological effects of variation of genes within the Idd3 region and for studying long-range chromosome remodeling.

Detailed description

This NOD congenic strain, commonly referred to as NOD.B6-Idd3, commonly referred to as NOD.B6-Idd3R450, is carrying Chromosome 3 alleles, rs3022959 through rs3140619, derived from strain C57BL/6 including the insulin dependent diabetes susceptibility 3 loci (Idd3). This NOD.B6 congenic strain is diabetes resistant, with approximately 10% of the females becoming diabetic by 250 days of age. Activated and non-activated thymocytes and splenocytes of this T1D protected stock produce more Il2 mRNA than T1D susceptible strains (Stock No's. 007930, 007931, and 007932). This congenic strain, one of a set of 5 strains (Stock No's. 007930, 007931, 007932, and 007933), has been useful to positionally clone Idd3, to study the biological effects of variation of genes within the Idd3 region, specifically the Il2 gene and continues to be valued for studying long-range chromosome remodeling.

Development

C57BL/6 (Type 1 diabetes resistant)-derived portions of the Idd3 locus, located on Chromosome 3, were introgressed onto the genetic background of NOD/MrkTac (Type 1 diabetes susceptible). Idd3 contains major candidate gene IL-2 as well as IL21, Tenr, Cetn4, and Fgf2. This strain was produced by mating mice from NOD/MrkTac to B6.Pl-Thy1^a/Cy followed by 12 additional crosses to NOD/MrkTac with selection for Idd3 markers. Siblings carrying the C57BL/6 derived chromosomal segment denoted by markers D3Nds55 (34.9Mb) through D3Nds76 (37.7Mb) were intercrossed to make homozygous. 5kSNP Chip Data based on NCBI, build 36, identifies the congenic interval between SNP's rs3022959 through rs3140619 with no other contamination on other chromosomes. This strain carries Thy1^b of NOD origin. In 2007, the T1DR received this strain at generation N13F25.

Allele

Symbol: Idd3^C57BL/6
Name: C57BL/6
MGI accession ID: MGI:2389019
Generation method: QTL
Marker symbol: Idd3
Marker name: insulin dependent diabetes susceptibility 3
Chromosome: 3
Strain of origin: C57BL/6
Molecular note: This allele confers resistance to insulin dependent diabetes compared to NOD.
General note: Idd3 and Idd5 appear to interact additively. C57BL/6-derived alleles at Idd3 in combination with C57BL/10-derived alleles at Idd5 partially reverses autoimmune exocrinopathy markers on an NOD genetic background.

Idd10 and Idd3 interact to promote disease resistance. Homozygosity for C57BL/6-derived alleles at both Idd10 and Idd3 confers significantly increased resistance to type 1 diabetes.

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 heterogenous IL-2 mobility pattern with major protein species ranging from 17-19 kDa while susceptible strains 129 and NOD display a homogenous IL-2 mobility pattern with one major protein species at approximately 21-22 kDa.