Idd11^NOD/ShiLt
QTL Variant Detail

Summary

• QTL variant: Idd11^NOD/ShiLt
• Name: insulin dependent diabetes susceptibility 11; NOD/ShiLt
• MGI ID: MGI:3036810
• QTL: Idd11 Location: Chr4:100604870-100605006 bp Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: NOD/ShiLt

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers susceptibility to insulin dependent diabetes compared to C57BL/6 and SJL. (J:19245)

Notes

Homozygosity for NOD/Lt-derived alleles confers susceptibility to type 1 diabetes.

Mapping and Phenotype information for this QTL, its variants and associated markers

J:60311

The authors generated three congenic strains to better define the Idd11 region on mouse Chromosome 4. Two of the strains had a significant decrease in the incidence of diabetes (P<0.001) compared NOD/Lt cntrol mice. The Idd11 locus was placed in a 13 cM interval between D4Mit119 and D4Mit204. The third congenic strain containing a B6 interval surronding the Slc9a1 locus was not protected against diabetes and eliminated the Slc9a1 as a candidate.

J:98145

Linkage analysis was performed on 192 animals from a (NOD/Bom x C57BL/6J)F2 intercross to map QTLs associated with B cell phenotypes. 119 polymorphic markers at an average spacing of 15 cM were used in the genome scan. Parental strain NOD/Bom is susceptible to type 1 diabetes and exhibits an expanded marginal zone (MZ) B cell population compared to the diabetes resistant parental strain C57BL/6J.

Peak linkage to CD21high B cell subsets mapped to 59.9 cM on mouse Chromosome 4 near D4Mit72 with LOD=4.4. This locus coincides with previously mapped diabetes QTL Idd11 (64.6 cM) and maps near previously identified QTL Idd9 (82 cM). The QTL interval spans a 7 cM region between D4Mit72 and D4Mit251 (66 cM) and explains approximately 12% of the phenotypic variance. Other previously identified QTLs mapping near Idd11 are Lbm1 (57.5 cM), Lbw2 (55.6 cM), and Sbw2 (44.5 cM).

Suggestive linkage to CD21high B cell subsets mapped to mouse Chromosome 1 (D1Mit498), mouse Chromosome 4 (D4Mit235), mouse Chromosome 9 (D9Mit205), and mouse Chromosome 19 (D19Mit91).

J:108004

NOD x C57BL/6J congenic (NOD.B6) mice were informative in confirming the mapping of Idd11 between D4Mit73 and D4Mit203.

References

• Original: J:19245 Morahan G, et al., Genetic and physiological association of diabetes susceptibility with raised Na+/H+ exchange activity. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5898-902
• All: 5 reference(s)