NOD.B-Idd5^C57Bl/10SnJIdd3^C57BL/6/6109MrkTacJ

Stock number: 012393
Product name: NOD.B-Idd3/5
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

This bi-congenic strain, R6109, is the result of crossing 2 congenic strains together and contains a C57BL/10SnJ derived segment containing Idd5.1, Idd5.2 and Idd5.3 on chromosome 1 and a second C57BL/6 derived segment containing Idd3 on chromosome 3. This strain may be useful to better understand the variation of diabetic resistance conferred by Idd loci; for studying long-range chromosome remodeling and for identifying diabetes susceptible candidate genes within the Idd5 subloci.

Detailed description

This NOD/MrkTac bicongenic strain carries C57BL/6 derived genome on Chr. 3 that contains Idd3 and C57BL/10SnJ derived genome on Chr. 1 containing Idd5.1, Idd5.2 and Idd5.3. No diabetes was observed in NOD.B-Idd3/5 congenic female mice by 7 months of age (Hunter et al. 2007) and are almost completely protected from insulitis and the occurrence insulin autoantibodies. .

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 Idd5 and for conducting mapping experiments to further define the Idd5 and Idd3 regions.

Development

NOD.B-Idd5^C57Bl/10JIdd3^C57BL/6J/6109MrkTacJ was developed through intercross of mice from NOD.B6-Idd3 (commonly referred to as NOD.B6-Idd3, line R450) to NOD.B10-Idd5.1, 5.2, 5.3 (commonly referred to as NOD.B10-Idd5, line R450; Stock No. 004344) and bred to homozygosity; testing for retention of the congenic intervals at each generation. This NOD/MrkTac bicongenic stock contains a C57BL/6 derived congenic interval on Chr. 3 containing Idd3 and defined within markers D3Nds36 (36.4Mb) and D3Nds34 (37.2Mb). The second congenic interval is a C57BL/10SnJ derived (Stock No. 000666), Chr. 1 segment, containing Idd5.1, 5.2, 5.3, defined by markers D1Mit124 (57.7Mb) through D1Mit132 (77.1 Mb). In 2011, the T1DR received this strain at generation N13F?.

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: 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.