NOD.CZI-Idd3^CZECHI/EiJ/MrkTacJ

Stock number: 007933
Product name: NOD.CZECH-Idd3
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

The 5 strains that comprise this NOD congenic set (Stock No.'s 007930, 007931, 007932, 007933, 007934) contain the Idd 3 region from non-NOD strains. All of these strains are viable and fertile. Stocks containing the Idd 3 region from SWR/J, A/J, or CAST/EiJ are diabetes susceptible, while the congenic stocks containing the Idd 3 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 Chr. 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.CZECH-Idd3, is carrying Chr 3 alleles, rs13477023 (20.01Mb) through rs13477134 (58.91Mb), derived from strain CZECH/EiJ including the insulin dependent diabetes susceptibility 3 loci (Idd3). Il2 exon 1 sequence and glycosylation pattern is similar to NOD/MrkTac. Surprisingly, the diabetes frequency of this strain of mice is identical to that of NOD.B6-Idd3 mice. Activated and non-activated thymocytes and splenocytes of this T1D protected stock produce 2 fold more Il2 mRNA than T1D susceptible strains (Stock No's. 007930, 007931, and 007932). However, the NOD.CZECH-Idd3 congenic produces more Il2 mRNA than the NOD.B6-Idd3 congenic. This congenic strain, one of a set of 5 strains (Stock No's 007930, 007931, 007932, and 007934), 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 continue to be valued for studying long-range chromosome remodeling.

Development

A CZECHI/EiJ (Stock No.002799) congenic segment is 32.9Mb in length and is defined within SNPs rs13477023 (20.01Mb) and rs13477134 (58.91Mb) that includes the Idd3 locus on Chr 3. Idd3 contains major candidate gene IL2 as well as IL21, Tenr, Cetn4 and Fgf2. CZECHI/EiJ mice are wild derived and have a greater diversity of sequence variants than inbred mice. The CZECHI/EiJ congenic segment was introgressed onto the NOD/MrkTac background. This strain was produced by mating mice from NOD/MrkTac to CZECHI/EiJ followed by 5 additional crosses to NOD/MrkTac with selection for Idd3 markers. Siblings carrying the CZECHI/EiJ derived segment denoted by makers D3Mit329 through D3Mit274 were intercrossed to make homozygous. 5K SNP Chip Data, based on NCBI, build 36, identifies the congenic interval between SNPs rs13477023 (20.01Mb) and rs13477134 (58.91Mb) in addition a contaminating 3.45Mb CZECHI/EiJ region on Chr 1 defined between SNPs rs13476237 (173.54Mb) and rs13478254 (176.99Mb) and SNP rs13476254 (176.99Mb) on Chr 13 was identified. In 2007, the T1DR received this strain at generation N6F25. Genetic quality control performed at The Jackson Laboratory did not identify the disclosed contamination identified by SNP's on Chr.'s 1 and 13 with the Mit markers that were used. However marker D18Mit208 has been identified as CZECH/EiJ in Origin.

Allele

Symbol: Idd3^CZECHI/EiJ
Name: CZECHI/EiJ
MGI accession ID: MGI:3764466
Generation method: QTL
Marker symbol: Idd3
Marker name: insulin dependent diabetes susceptibility 3
Chromosome: 3
Strain of origin: CZECHI/EiJ
Molecular note: This allele confers resistance to type 1 diabetes compared to A/J, CAST/EiJ, NOD, and SWR/J. The diabetes frequency of this strain of mice is identical to that of NOD.B6-Idd3 mice.