NOD.B10Sn-Idd5^C57BL/10SnJ/1092MrkJ

Stock number: 008893
Product name: NOD.B10-Idd5R2
Strain synonyms: NOD.B10-Idd5, line R2, NOD.B10-Idd5, line R1092, NOD.B10-<Idd5R2>, 1092, R2
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These NOD congenic strains, Stock No. 008893 and 008894, are the result of crossing segments of C57BL/10SnJ derived Chromosome 1 into the NOD/MrkTac background. These strains may be useful to better understand the variation of diabetic resistance conferred by Idd loci and should be useful for identifying diabetes susceptible candidate genes within the Idd5 subloci, specifically Idd5d.

Detailed description

This NOD congenic strain, commonly referred to as NOD.B10-Idd5, line R2 (also known as line 1092), carries two C57BL/10SnJ (Stock No. 000666) Chromosome 1 segments. The first proximal segment is defined within D1Mit5 (63.8Mb) and D1Mit101 (147.31Mb) that includes the insulin dependent diabetes susceptibility (Idd) 5.2, 5.3 and part of the Idd5.4 loci (Idd5b, Idd5c, and Idd5d, respectively). The second distal segment is defined within D1Mit346 (152.63Mb) and D1Mit267 (157.94Mb) and contains the remainder of the Idd5.4 (Idd5d) region. This strain differs from its sister strain, NOD.B6-Idd5^C57BL/10SnJ/974MrkJ (Stock No. 008894), in that both Cd28 and Ctla4 are NOD in origin. Diabetes incidence among 200-day old female mice of this strain has been reported at 70%, compared with more than 80% in NOD controls (Hunter, et al. 2007), and males also become diabetic (incidence not done). This strain is key to understanding the variation in diabetic resistance conferred by Idd loci, in particular the epistatic interactions of Idd5.1 alleles with alleles at Idd5.4.

This strain and NOD.B10Sn-Idd5, line 974 (Stock No. 008894) together define the Idd5.1 interval.

This strain may be useful for positional mapping of the Idd5.4 loci and identifying candidate genes within the Idd5.4 region.

Development

This NOD/MrkTac congenic stock contains two genomic segments from C57BL/10SnJ introgressed into Chromosome 1. The first segment, 83.65Mb in length is defined within markers D1Mit5, 63.8Mb and D1Mit101, 147.31Mb contains Idd5.2, Idd5.3 and part of Idd5.4, a newly identified B10 diabetes susceptible region. The major candidate gene for Idd5.2 is Nramp1; and Idd5.3 is Acadl. The second, distal, segment is 5.31Mb in length and is defined within D1Mit346, 152.63Mb through D1Mit267, 157.94Mb and contains the remainder of the Idd5.4 region. Mating mice from NOD/MrkTac to C57BL/10SnJ followed by 10 additional crosses to NOD/MrkTac with selection for markers on Chromosome 1 produced this strain. Siblings carrying the C57BL/10SnJ derived segments denoted by markers D1Mit5 through D1Mit101 and D1Mit346 through D1Mit267 were intercrossed to make homozygous. 5kSNP Chip Data, based on NCBI, build 37, identifies no C57BL/10SnJ genetic contamination of other chromosomes. In 2009, the Type 1 Diabetes Resource received this strain at generation N11F35.

Allele

Symbol: Idd5^C57BL/10SnJ
Name: C57BL/10SnJ
MGI accession ID: MGI:3036897
Generation method: QTL
Marker symbol: Idd5
Marker name: insulin dependent diabetes susceptibility 5
Chromosome: 1
Strain of origin: C57BL/10SnJ
Molecular note: This allele confers resistance to insulin dependent diabetes compared to NOD/MrkTac.
General note: Idd3 and Idd5 appear to interact additively. C57BL/6-derived alleles at Idd3 in combination with C57BL/10SnJ-derived alleles at Idd5 partially reverses autoimmune exocrinopathy markers on an NOD genetic background.

Allele

MGI accession ID: MGI:3830820
Marker symbol: Idd5.3
Marker name: insulin dependent diabetes susceptibility 5.3
Chromosome: 1

Allele

MGI accession ID: MGI:2158434
Marker symbol: Idd5.2
Marker name: insulin dependent diabetes susceptibility 5.2
Chromosome: 1

Allele

MGI accession ID: MGI:3830821
Marker symbol: Idd5.4
Marker name: insulin dependent diabetes susceptibility 5.4
Chromosome: 1