Congenic animals were created to observe the effect of diabetes QTL Idd1 on mouse Chromosome 17. The congenic NOD.CTS-H2 carries CTS-derived DNA at the H2 locus, which is part of Idd1, on an NOD diabetes-susceptible genetic background. Parental strain CTS is diabetes resistant but shares the same H2 alleles as NOD. Interestingly the NOD.CTS-H2 congenic is susceptible to diabetes but with lower incidence compared to NOD. Authors state that the H2 locus is responsible for the diabetes susceptible effect ofIdd1 but does not explain it entirely. A closely linked but distinct QTL, Idd16 at 18 cM, may also contribute to the NOD susceptible phenotype. A candidate gene for Idd16 is Tnf (19.06 cM). Haplotype analysis was performed to assess the candidacy of Tnf.The non-diabetic inbred strain NON shares the same Tnf alleles as the diabetic strain NOD. The congenic NON.NOD-H2 carryies NON-derived DNA around the H2 locus (including Tnf) on a NOD genetic background and is diabetes susceptible. This data supports the candidacy of Tnf for Idd16.
To study the Idd3 candidate gene, Il2 (19.2 cM on mouse Chromosome 3), a congenic line was constructed. NOD.IIS-Il2 carries ISS-derived DNA at Il2 on an NOD diabetes susceptible background. Parental strain ISS is resistant to diabetes but shares alleles with NOD at Il2. The congenic is phenotypically indistinguishable from the NOD parental indicating that the NOD alleles at Il2 exert an effect on diabetes susceptibility. Another candidate gene for Idd3 is Il21. Il21 is closelylinked to and forms a haplotype with Il2, making Il21 a strong candidate for Idd3.
Idd10 maps to 48.5 cM on mouse Chromosome 3. Fcgr1 (45.2 cM) has been identified as a possible candidate gene for Idd10. Sequence analysis revealed 17 amino acid differences between NOD and C57BL/10 in addition to deletion of 75% of the cytoplasmic tail. A congenic line carrying diabetes resistant ISS-derived DNA at Idd10 on an NOD diabetes susceptible background was constructed. However, the NOD.IIS-Idd10 congenic is notsusceptible to diabetes, therefore excluding Fcgr1 from the candidate gene list. Further analysis of the Idd10 locus revealed 3 multiply linked loci: Idd10, Idd17, and Idd18.