NOD.B6-Idd3^C57BL/6 Idd10^C57BL/6J Idd18^C57BL/6/1538MrkTacJ

Stock number: 013185
Product name: NOD.B6-Idd3/10/18 R1538
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

This strain is one of a set of 3 NOD.B6 congenic Idd10 and Idd18 strains (Stock No. 013186, 013187). Stocks 13185, 13186 and 13187 resulted from crossing segments of C57BL/6J derived chromosome 3 into the NOD/MrkTac background. Mice of this congenic NOD strain contain C57BL/6J derived Idd3, Idd10, Idd18.1, Idd18.2 and Idd18.3 regions. These strains may be useful to better understand the variation of diabetic resistance conferred by Idd loci and may be useful for identifying diabetes susceptible candidate genes within the Idd18 subloci.

Detailed description

This NOD/MrkTac bi-congenic strain, commonly referred to as NOD.B6-Idd3/10/18R323, line 1538 is viable and fertile. Mice of this strain contain 2 C57BL/6J genomic segments from the diabetes resistant strain C57BL/6J (Stock No. 000664) introgressed into the NOD chromosome 3. The C57BL/6 genomic segments include Idd3, Idd10, Idd18.1, Idd18.2 and Idd18.3, while the Idd17 region is of NOD origin. The Idd3 region contains major candidate gene Il2 (37Mb); the Idd10 region contains major candidate gene Cd101 (100Mb); the Idd18.1 region contains major candidate gene Vav3 (109Mb) and the recently identified 966Kb Idd18.3 region contains 22 genes and 1 pseudogene. Congenic female mice are completely protected from diabetes at 7-months of age.
This strain is useful for understanding the variation in diabetic resistance conferred by Idd loci, in particular the epistatic interactions of Idd3 alleles with alleles at Idd18.

Development

This strain was produced by mating mice from NOD/MrkTac (NOD) to C57BL/6J followed by 11 additional crosses to NOD with selection for chromosome 3, Idd3, Idd10, Idd18.1, Idd18.2 and Idd18.3 markers. Siblings carrying the C57BL/6J derived segments denoted by markers D3Mit167 (32Mb) through D3Mit94 (40Mb) and D3Mit12 (100Mb) through RS538124092 (122Mb) were intercrossed to make homozygous. 5kSNP Chip Data, based on NCBI, build 36, identifies no C57BL/6J genetic contamination of other chromosomes. In 2010, the Type 1 Diabetes Resource received this strain at generation N12F8.

Allele

Symbol: Idd18^C57BL/6
Name: C57BL/6
MGI accession ID: MGI:3036823
Generation method: QTL
Marker symbol: Idd18
Marker name: insulin dependent diabetes susceptibility 18
Chromosome: 3
Strain of origin: C57BL/6
Molecular note: This allele confers resistance to insulin dependent diabetes compared to NOD.
General note: Idd10 and Idd18 interact to promote disease resistance. Homozygosity for C57BL/6-derived alleles at both Idd10 and Idd18 confers significantly increased resistance to type 1 diabetes.

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.

Allele

Symbol: Idd10^C57BL/6J
Name: C57BL/6J
MGI accession ID: MGI:3038835
Generation method: QTL
Marker symbol: Idd10
Marker name: insulin dependent diabetes susceptibility 10
Chromosome: 3
Strain of origin: C57BL/6J
Molecular note: This allele confers resistance to insulin dependent diabetes compared to NOD.
General note: Idd10 and Idd18 interact to promote disease resistance. Homozygosity for C57BL/6-derived alleles at both Idd10 and Idd18 confers significantly increased resistance to type 1 diabetes.

Idd10 and Idd17 interact to promote disease resistance. Homozygosity for C57BL/6-derived alleles at both Idd10 and Idd17 confers significantly increased resistance to type 1 diabetes.

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.