NOD.A-Idd3^A/J/MrkJ

Stock number: 007931
Product name: NOD.A/J-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. 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.A/J-Idd3, is carrying Chr 3 alleles, SNPS rs168642 (18.178Mb) through rs13477164, (66.638Mb) derived from strain A/J including the insulin dependent diabetes susceptibility 3 loci (Idd3). Diabetes onset and incidence among mice of this strain is reported to be similar to NOD/MrkTac, with approximately 65% of the females becoming diabetic by 200 days of age. The congenic NOD.A/J-Idd3 females are predisposed to autoimmune ovarian dysgenesis. Thymocytes and splenocytes, either non-activated or activated of this T1D susceptible stock produce less Il2 mRNA than T1D protected strains (Stock No's. 007933 and 007934). Il2 molecules derived from the A/J strain are identical to NOD. This congenic strain, one of a set of 5 strains (007930, 007932, 007933 and 007934), has been useful to positionally clone Idd3 and to study the biological effects of variation of genes within the Idd3 region, specifically the Il2 and continue to be valued for studying long-range chromosome remodeling.

Development

An A/J (Stock No. 000646) congenic segment 47.69Mb in length is defined within SNPs rs168642 (18.178Mb) and rs13477164 (66.638Mb) that includes the Idd3 locus on Chr 3. Idd3 contains major candidate gene IL2 as well as IL21, Tenr, Cetn4 and Fgf2. The A/J congenic segment was introgressed onto the NOD/MrkTac background. This strain was produced by mating mice from NOD/MrkTac to A/J followed by 5 additional crosses to NOD/MrkTac with selection for Idd3 markers. Siblings carrying the A/J derived segment denoted by makers D3Mit329 through D3Mit274 were intercrossed to make homozygous. 5kSNP Chip Data, based on NCBI, build 36, identifies the congenic interval between SNPs rs6168642 (18.46Mb) and rs13477164 (66.15Mb) with no genetic contamination of other chromosomes. In 2007, the T1DR received this strain at generation N6F11.

Allele

Symbol: Idd3^A/J
Name: A/J
MGI accession ID: MGI:3764460
Generation method: QTL
Marker symbol: Idd3
Marker name: insulin dependent diabetes susceptibility 3
Chromosome: 3
Strain of origin: A/J
Molecular note: This allele confers susceptibility to type 1 diabetes compared to C57BL/6J and CZECHI/EiJ. Diabetes onset and incidence among mice of this strain is reported to be similar to NOD/MrkTac mice.