These doubly congenic mice carry two chromosomal segments bounded by Mit markers: one segment from Chromosome 17 that includes the major histocompatibility complex (H2) and the insulin dependent diabetes susceptibility locus 1 (Idd1), and the other segment from Chromosome 6 containing the insulin dependent diabetes susceptibility locus 6 (Idd6).
|Allele Type||Gene Symbol||Gene Name|
|QTL||Idd1||insulin dependent diabetes susceptibility 1|
|Allele Type||Gene Symbol||Gene Name|
|Not Applicable||H2||histocompatibility-2, MHC|
|Allele Type||Gene Symbol||Gene Name|
|QTL||Idd6||insulin dependent diabetes susceptibility 6|
|Marker Symbol||Marker Name|
|D6Mit54||DNA segment, Chr 6, Massachusetts Institute of Technology 54|
|D17Mit10||DNA segment, Chr 17, Massachusetts Institute of Technology 10|
|D6Mit14||DNA segment, Chr 6, Massachusetts Institute of Technology 14|
|D17Mit21||DNA segment, Chr 17, Massachusetts Institute of Technology 21|
This strain is doubly congenic for a 19 cM segment of Chr 17 (called c17 in Yui et al.) extending from D17Mit21through D17Mit10and including the major histocompatibility complex, H2,and the insulin dependent diabetes susceptibility locus Idd1and for a 24 cM segment (called c6 by Yui et al.)of Chr 6 extending from D6Mit54through D6Mit14and including the insulin dependent diabetes susceptibility locus Idd6.No information has been published for this double congenic strain. However, upon histologic examination of the pancreas, a significantly higher percentage of B6.NOD-(D17Mit21-D17Mit10) singly congenic mice than of C57BL/6J control mice were found to exhibit periinsulitis, and more extensive mononuclear cell infiltrates were observed in the pancreata 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. Incidence and severity of periinsulitis in B6.NOD-(D6Mit54-D6Mit14) mice were similar to those of controls. Male and female B6.NOD-(D17Mit21-D17Mit10) mice exhibited similar incidence of pancreatic infiltration; female NOD mice are more susceptible than males to both insulitis and diabetes.
Genomic segments found in earlier linkage studies to include diabetogenic loci were transferred in the laboratory of E.K. Wakeland from NOD/Uf to C57BL/6 by six successive backcrosses (to N7). Sibs of each lineage were then intercrossed to generate mice homozygous for each segment. Microsatellite analysis was used to type mice for loci in the regions of interest. The B6.NOD-(D6Mit54-D6Mit14) (D17Mit21-D17Mit10) double congenic strain was created by crossing mice of the singly congenic B6.NOD-(D17Mit21-D17Mit10) and B6.NOD-(D6Mit54-D6Mit14) strains, then breeding to homozygosity for both congenic segments.
|Gene Symbol and Name||Idd1, insulin dependent diabetes susceptibility 1|
|Strain of Origin||NOD/Uf|
|General Note||NOD is homozygous for recessive alleles for susceptibility at all three loci, Idd1s, Idd2s, and Idd3s. The dominant alleles for non-susceptibility to IDD, Idd1r, 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.
|Molecular Note||This allele confers increased periinsulitis and increased CD4 lymphocytosis compared to C57BL/6.|
|Allele Name||g7 variant|
|Allele Type||Not Applicable|
|Allele Synonym(s)||H-2g7; H-2g7|
|Gene Symbol and Name||H2, histocompatibility-2, MHC|
|Strain of Origin||Not Applicable|
|General Note||The g7 variant has been observed in the following strains: DBR7, NON.NOD-H2g7|
|Gene Symbol and Name||Idd6, insulin dependent diabetes susceptibility 6|
|Strain of Origin||NOD|
|General Note||This allele also confers defective IFN-gamma response in NK cells on a C57BL/6 genetic background (J:85823).|
|Molecular Note||This allele confers impaired thymocyte proliferation compared to C57BL/6.|
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