Summary
It has been suggested that one of the recessive genes controlling diabetes in non-obese diabetic mice is linked to the major histocompatibility complex. We, therefore, performed restriction fragment length polymorphism studies of major histocompatibility complex genes (class I, II, and III) in non-obese diabetic mice in comparison with those of their non-diabetic sister strains, non-obese non-diabetic, cataract, and ILI mice which were derived from the same Jcl-ICR mice as the non-obese diabetic mouse was. When class II and III probes and a minimum of four restriction enzymes were used, class II and III genes of non-obese diabetic mice were indistinguishable from those of cataract and ILI mice but totally different from those of non-obese non-diabetic mice. The studies also indicated that Aβ, Eβ, and C4-Slp genes of non-obese diabetic, cataract, and ILI mice, and Aα, Aβ, Eβ and C4-Slp genes of non-obese non-diabetic mice are different from those of BALB/c and C57BL/6 mice, respectively. While non-obese non-diabetic mice expressed the Eα gene, non-obese diabetic, cataract, and ILI mice appeared to carry a deletion in the 5′ end of the Eα gene resulting in failure to transcribe the Eα gene. When class I probe was used, cataract mice showed very different band patterns from those of the other ICR-derived mice. It is suggested that non-obese diabetic, non-obese non-diabetic, and ILI mice contain only a single class I D region gene. Taken together, these results indicate that, although class I loci of non-obese diabetic and ILI mice were serologically typed as Kd and Db, and those of non-obese non-diabetic mice were typed as Kb and Db, no H-2g type recombination between K and D loci of non-obese diabetic, cataract, and ILI mice was evident. Since cataract and ILI mice are suggested to share the same class II and III regions with non-obese diabetic mice, they should be feasible strains for further studies to characterise the major histocompatibility complex-linked diabetogenic gene(s) of the non-obese diabetic mouse strain.
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Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y (1980) Breeding of a non-obese, diabetic strain of mice. Exp Animal (Tokyo) 29: 1–13
Fujita T, Yui R, Kusumoto Y, Serizawa Y, Makino S, Tochino Y (1982) Lymphocytic insulitis in a “non-obese diabetic (NOD” strain of mice: an immunohistochemical and electron microscope investigation. Biomed Res 3: 429–443
Kanazawa Y, Komeda K, Sato S, Mori S, Akanuma Y, Takaku F (1984) Non-obese-diabetic mice: immune mechanisms of pancreatic B-cell destruction. Diabetologia 27: 113–115
Maruyama T, Takei I, Taniyama M, Kataoka K, Matsuki S (1984) Immunological aspect of non-obese diabetic mice: immune islet cell-killing mechanism and cell mediated immunity. Diabetologia 27: 121–123
Yokono K, Shii K, Hari J, Yaso S, Imamura Y, Ejiri K, Ishihara K, Fuji S, Kazumi T, Taniguchi H, Baba S (1984) Production of monoclonal antibodies to islet cell surface antigens using hybridisation of spleen lymphocytes from non-obese diabetic mice. Diabetologia 26: 379–385
Yoshida TO, Koide Y, Fujishima Y, Hori T, Masamoto T, Wu CL, Haraguchi S, Nishimura M (1987) Gene modification and autoimmune mechanisms in NOD mouse strain as human IDDM model. In: Wigzell H, Kyogoku M (eds) New horizons in animal models for autoimmune diseases. Academic Press, Tokyo, pp 59–67
Makino S, Muraoka Y, Kishimoto Y, Hayashi Y (1985) Genetic analysis for insulitis in NOD mice. Exp Animal 34: 425–432
Hattori M, Buse JB, Jackson RA, Glimcher L, Dorf ME, Minami M, Makino S, Moriwaki K, Kuzuya H, Imura H, Strauss WM, Seidman JG, Eisenbarth GS (1986) The NOD mouse: recessive diabetogenic gene in the major histocompatibility complex. Science 231: 733–735
Prochazka M, Leiter EH, Serreze DV, Coleman DL (1987) Three recessive loci required for insulin dependent diabetes in nonobese diabetic mice. Science 237: 286–289
Wicker LS, Miller BJ, Coker LZ, McNally SE, Scott S, Mullen Y, Appel MC (1987) Genetic control of diabetes and insulitis in the nonobese diabetic (NOD) mouse. J Exp Med 165: 1639–1654
Acha-Orbea H, McDevitt HO (1987) The first external domain of the nonobese diabetic mouse class II I-Aβ chain is unique. Proc Natl Acad Sci USA 84: 2435–2439
Nishimoto H, Kikutani H, Yamamura K, Kishimoto T (1987) Prevention of autoimmune insulitis by expression of I-E molecule in NOD mice. Nature 328: 432–434
Steinmetz M, Minard K, Horvath S, McNicholas J, Srelinger J, Wake C, Long E, Mach B, Hood L (1982) A molecular map of the immune response region from the major histocompatibility complex of the mouse. Nature 300: 35–42
Stephan D, Sun H, Lindahl KF, Meyer E, Hammering G, Hood L, Steinmetz M (1986) Organization and evolution of D region class I genes in the mouse major histocompatibility complex. J Exp Med 163: 1227–1244
Evans GA, Margulies DH, Shykind B, Seidman JG, Ozato K (1982) Exon shuffling: Mapping polymorphic determinants on hybrid mouse transplantation antigens. Nature 300: 755–757
Nonaka M, Nakayama K, Yeul YD, Schimizu A, Takahashi M (1985) Molecular cloning and characterization of complementary and genomic DNA clones for mouse C4 and Slp. Immunol Rev 87: 81–99
Nasmyth KA (1982) The regulation of yeast mating-type chromatin structure by SIR: an action at a distance affecting both transcription and transposition. Cell 30: 567–578
Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from source enriched in ribonuclease. Biochemistry 18: 5294–5299
Steinmetz M, Malissen M, Hood L, Orn A, Maki RA, Dastoornikoo QR, Stephan D, Gibb E, Romaniuk R (1984) Tracts of high or low sequence divergence in the mouse major histocompatibility complex. EMBO 33: 95–3003
Larhammer DD, Hammerling U, Denaro M, Lund T, Flavell RA, Rask L, Peterson PA (1983) Structure of the murine immune response I-Aβ locus: Sequence of the I-Aβ gene and an adjacent β-chain second domain exon. Cell 34: 179–188
Widera G, Flavell RA (1985) The I region of the C57BL/10 mouse: Characterization and physical linkage to H-2K of an SB β-like class II pseudogene, ψA β3: Proc Natl Acad Sci USA 82: 5500–5504
Denbic Z, Ayane M, Klein J, Steinmetz M, Benoist CO, Mathis DJ (1985) Inbred and wild mice carry identical deletions in their Eα MHC genes. EMBO J 4: 127–131
Hyldig-Nielsen JJ, Schenning L, Hammerling U, Widmark E, Heldin E, Lind P, Servenius B, Lund T, Fravell R, Lee JS, Trowsdale J, Schreier PH, Zablitzky F, Larhammer D, Peterson PA, Rask L (1983) The complete nucleotide sequence of the I-Eαd immune response gene. Nucleic Acids Res 11: 5055–5071
Mathis DJ, Benoist CO, Williams VEII, Kanter MR, McDevitt HO (1983) Several mechanisms can account for defective Eα gene expression in different mouse haplotypes. Proc Natl Acad Sci USA 80: 273–277
Steinmetz M, Winoto A, Minard K, Hood L (1982) Clusters of genes encoding mouse transplantation antigens. Cell 28: 489–498
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Fujishima, Y., Koide, Y., Kaidoh, T. et al. Restriction fragment length polymorphism analysis of major histocompatibility complex genes in the non-obese diabetic mouse strain and its non-diabetic sister strains. Diabetologia 32, 118–125 (1989). https://doi.org/10.1007/BF00505184
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DOI: https://doi.org/10.1007/BF00505184