Abstract
Multiple genes control the development of autoimmune diabetes both in humans and in the nonobese diabetic (NOD) strain of mouse. Previously, three insulin-dependent diabetes (Idd) genes, Idd3, Idd10, and Idd17, were localized to mouse Chromosome (Chr) 3. The B10-or B6-derived resistance alleles at Idd10 and Idd3 together provide the NOD mouse with nearly complete protection from diabetes. In the present study, the 10.2-cM region encoding Idd10 was defined further with newly developed congenic strains. A locus, located in the centromeric 2.1 cM of the 10.2 cM region, contributed to the Idd10 trait. However, this locus did not account for the full effect of Idd10, suggesting the presence of a second gene in the distal portion of the 10.2-cM region. This second gene is designated as Idd18 and is localized to a 5.1-cM region. The resolution of the originally defined Idd3 locus into at least four separate loci, Idd3, Idd10, Idd17, and Idd18, illustrates the complex poly genic nature of diabetes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Denny P, Lord CJ, Hill NJ, Goy JV, Levy ER, Podolin PL, Peterson LB, Wicker LS, Todd JA, Lyons PA (1997) Mapping of the IDDM locus, Idd3 to a 0.35-cM interval containing the Interleukin-2 gene. Diabetes 46, 695–700
Ghosh S, Palmer S, Rodrigues N, Cordell H, Hearne C, Cornall R, Prins J-B, McShane P, Lathrop G, Peterson L, Wicker L, Todd J (1993) Polygenic control of autoimmune diabetes in nonobese diabetic mice. Nat Genet 4, 404–409
Ikegami H, Makino S, Yamato E, Kawaguchi Y, Ueda H, Sakamoto T, Takekawa K, Ogihara T (1995) Identification of a new susceptibility locus for insulin-dependent diabetes mellitus by ancestral haplotype congenic mapping. J Clin Invest 96, 1936–1942
Lord CJ, Bohlander SK, Hopes EA, Montague CT, Hill NJ, Prins J-B, Renjilian RJ, Peterson LB, Wicker LS, Todd JA, Denny P (1995) Mapping the diabetes polygene Idd3 on mouse chromosome 3 by use of novel congenic strains. Mamm Genome 6, 563–570
Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y (1980) Breeding of a non-obese diabetic strain of mice. Exp Anim 29, 1–13
Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16, 7738
Podolin PL, Denny P, Lord CJ, Hill NJ, Todd JA, Peterson LB, Wicker LS, Lyons PA (1997) Congenic mapping of the insulin dependent diabetes (Idd) gene, Idd10, localizes two genes mediating the Idd10 effect, and eliminates the candidate Fcgrl. J Immunol 159, 1835–1843
Sundvall M, Jirholt J, Yang H-T, Jansson L, Engström Å, Pettersson U, Holmdahl R (1995) Identification of murine loci associated with susceptibility to chronic experimental autoimmune encephalomyelitis. Nat Genet 10, 313–317
Tochino Y (1987) The NOD mouse as a model of type 1 diabetes. CRC Crit Rev Immunol 8, 49–81
Todd JA, Aitman TJ, Cornall RJ, Ghosh, S, Hall JRS, Hearne CM, Knight AM, Love JM, McAleer MA, Prins J-B, Rodrigues N, Lathrop M, Pressey A, DeLarato NH, Peterson LB, Wicker LS (1991) Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature 351, 542–547
Wicker LS, Todd JA, Prins J-B, Podolin PL, Renjilian RJ, Peterson LB (1994) Resistance alleles at two non-major histocompatibility complex-linked insulin-dependent diabetes loci on chromosome 3, Idd3 and Idd10, protect nonobese diabetic mice from diabetes. J Exp Med 180, 1705–1713
Wicker LS, Todd JA, Peterson LB (1995) Genetic control of autoimmune diabetes in the NOD mouse. Annu Rev Immunol 13, 179–200
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Podolin, P.L., Denny, P., Armitage, N. et al. Localization of two insulin-dependent diabetes (Idd) genes to the Idd10 region on mouse Chromosome 3. Mammalian Genome 9, 283–286 (1998). https://doi.org/10.1007/s003359900749
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s003359900749