B6.NOD-(D1Mit3-Bcl2) (D17Mit21-D17Mit10)/LtJ

Stock number: 003069
Product name: B6.NOD Idd1,5 (c1c)
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These doubly congenic mice carry two chromosomal segments, one bound by an Mit marker and B-cell leukemia/lymphoma 2 (Bcl2) and the other by Mit markers. One segment from Chromosome 17 includes the major histocompatibility complex (H2) and the insulin dependent diabetes susceptibility locus 1 (Idd1), and the other segment from Chromosome 1 contains the insulin dependent diabetes susceptibility locus 5 (Idd5).

Detailed description

This strain is doubly congenic for a 19 cM segment of Chr 17 (called c17 in the reference below) extending from D17Mit21 through D17Mit10 and including the major histocompatibility complex, H2, and the insulin dependent diabetes susceptibility locus Idd1 and for a 44 cM segment of Chr 1 (called c1c by Yui et al.) extending from D1Mit3 through Bcl2 (B-cell leukemia/lymphoma 2) and including Idd5(insulin dependent diabetes susceptibility 5). No information has been published for this double congenic. However, upon histologic examination of the pancreas, a significantly higher percentage of both B6.NOD-D1Mit3-Bcl2 (Idd5) and B6.NOD-D17Mit21-D17Mit10 (H2^g7, Idd1) singly congenic mice than of C57BL/6J control mice were found to exhibit periinsulitis, and more extensive mononuclear cell infiltrates were observed in the pancreas of these mice. The pancreatic infiltrates were not associated specifically with the islets. Insulitis (intraislet infiltration) was extremely rare, and no more than one affected islet was observed in a single animal, even in cases where extensive perivascular/periductal infiltrates existed. Although male and female B6.NOD-D17Mit21-D17Mit10 (H2^g7, Idd1) mice exhibited similar incidence of pancreatic infiltration, B6.NOD-D1Mit3-Bcl2 (Idd5) females developed periinsulitis at twice the frequency of males. Female NOD mice are more susceptible than males to both insulitis and diabetes.

Development

Genomic segments found in earlier linkage studies to include diabetogenic loci were transferred from NOD/Uf to C57BL/6 by six successive backcrosses (to N7). Sibs of each lineage were then intercrossed to generate homozygotes for each segment. Microsatellite analysis was used to type mice for loci in the regions of interest. As evidence suggested the existence of multiple loci on Chr 1 that affect susceptibility to IDD and/or insulitis, two congenic lines were generated carrying overlapping segments of Chr 1, each including the diabetes susceptibility locus and one insulitis susceptibility locus. The B6.NOD-D1Mit3-Bcl2 D17Mit21-D17Mit10 (Idd5; H2^g7 , Idd1) double congenic strain was created by crossing mice of the singly congenic B6.NOD-D17Mit21-D17Mit10 (H2^g7 , Idd1) and B6.NOD-D1Mit3-Bcl2 (Idd5) strains, then breeding to homozygosity for both congenic segments.

Allele

Symbol: Idd1^NOD/Uf
Name: NOD/Uf
MGI accession ID: MGI:3037293
Generation method: QTL
Marker symbol: Idd1
Marker name: insulin dependent diabetes susceptibility 1
Chromosome: 17
Strain of origin: NOD/Uf
Molecular note: This allele confers increased periinsulitis and increased CD4 lymphocytosis compared to C57BL/6.
General note: NOD is homozygous for recessive alleles for susceptibility at all three loci, Idd1^s, Idd2^s, and Idd3^s. The dominant alleles for non-susceptibility to IDD, Idd1^r, etc., occur in the NON strain. Homozygosity for the recessive alleles at all three loci is necessary for the development of IDD.The Idd1 locus is linked to the major histocompatibility locus on Chr 17, but Idd2 is on Chr 9 (1) and Idd3 is on Chr 3 (J:8783, J:3351).

This locus is also linked to peripheral CD4 lymphocytosis.

Allele

Symbol: H2^g7
Name: g7 variant
MGI accession ID: MGI:3579321
Generation method: Not Applicable
Marker symbol: H2
Marker name: histocompatibility-2, MHC
Chromosome: 17
Strain of origin: Not Applicable
General note: The g7 variant has been observed in the following strains: DBR7, NON.NOD-H2^g7

Allele

Symbol: Idd5^NOD
Name: NOD
MGI accession ID: MGI:2389017
Generation method: QTL
Marker symbol: Idd5
Marker name: insulin dependent diabetes susceptibility 5
Chromosome: 1
Strain of origin: NOD
Molecular note: This allele confers susceptibility to insulin dependent diabetes compared to C57BL/10.

Allele

MGI accession ID: MGI:90738
Marker symbol: D17Mit10
Marker name: DNA segment, Chr 17, Massachusetts Institute of Technology 10
Chromosome: 17

Allele

MGI accession ID: MGI:91682
Marker symbol: D1Mit3
Marker name: DNA segment, Chr 1, Massachusetts Institute of Technology 3
Chromosome: 1

Allele

MGI accession ID: MGI:88138
Marker symbol: Bcl2
Marker name: B cell leukemia/lymphoma 2
Chromosome: 1

Allele

MGI accession ID: MGI:90809
Marker symbol: D17Mit21
Marker name: DNA segment, Chr 17, Massachusetts Institute of Technology 21
Chromosome: 17