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. 1987 Apr;84(8):2435–2439. doi: 10.1073/pnas.84.8.2435

The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique.

H Acha-Orbea, H O McDevitt
PMCID: PMC304666  PMID: 2882518

Abstract

The nonobese diabetic mouse is recognized as an important animal model for human insulin-dependent diabetes mellitus. One of the components of susceptibility to this disease has been mapped to the major histocompatibility complex. In this study, full-length cDNA clones encoding the I-A alpha and beta chains from the nonobese diabetic mouse have been isolated and sequenced. They are identical to the sequences previously determined from the H-2d haplotype except for the sequence encoding the first external domain, the leader peptide, and the 5' untranslated region of the I-A beta chain molecule. Most strikingly, there are five consecutive nucleotide substitutions which lead to two radical amino acid changes in a region that is conserved between human and mouse. We suggest that the unique structure of the first external I-A beta chain domain is a major determinant in the disease susceptibility that maps to the major histocompatibility complex of the nonobese diabetic mouse.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benoist C. O., Mathis D. J., Kanter M. R., Williams V. E., 2nd, McDevitt H. O. Regions of allelic hypervariability in the murine A alpha immune response gene. Cell. 1983 Aug;34(1):169–177. doi: 10.1016/0092-8674(83)90147-2. [DOI] [PubMed] [Google Scholar]
  2. Benoist C. O., Mathis D. J., Kanter M. R., Williams V. E., 2nd, McDevitt H. O. The murine Ia alpha chains, E alpha and A alpha, show a surprising degree of sequence homology. Proc Natl Acad Sci U S A. 1983 Jan;80(2):534–538. doi: 10.1073/pnas.80.2.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Choi E., McIntyre K., Germain R. N., Seidman J. G. Murine I-A beta chain polymorphism: nucleotide sequences of three allelic I-A beta genes. Science. 1983 Jul 15;221(4607):283–286. doi: 10.1126/science.6407114. [DOI] [PubMed] [Google Scholar]
  5. Davis M. M., Cohen D. I., Nielsen E. A., Steinmetz M., Paul W. E., Hood L. Cell-type-specific cDNA probes and the murine I region: the localization and orientation of Ad alpha. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2194–2198. doi: 10.1073/pnas.81.7.2194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Estess P., Begovich A. B., Koo M., Jones P. P., McDevitt H. O. Sequence analysis and structure-function correlations of murine q, k, u, s, and f haplotype I-A beta cDNA clones. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3594–3598. doi: 10.1073/pnas.83.11.3594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fritz R. B., Skeen M. J., Chou C. H., Garcia M., Egorov I. K. Major histocompatibility complex-linked control of the murine immune response to myelin basic protein. J Immunol. 1985 Apr;134(4):2328–2332. [PubMed] [Google Scholar]
  8. Germain R. N., Malissen B. Analysis of the expression and function of class-II major histocompatibility complex-encoded molecules by DNA-mediated gene transfer. Annu Rev Immunol. 1986;4:281–315. doi: 10.1146/annurev.iy.04.040186.001433. [DOI] [PubMed] [Google Scholar]
  9. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  10. Hattori M., Buse J. B., Jackson R. A., Glimcher L., Dorf M. E., Minami M., Makino S., Moriwaki K., Kuzuya H., Imura H. The NOD mouse: recessive diabetogenic gene in the major histocompatibility complex. Science. 1986 Feb 14;231(4739):733–735. doi: 10.1126/science.3003909. [DOI] [PubMed] [Google Scholar]
  11. Ikehara S., Ohtsuki H., Good R. A., Asamoto H., Nakamura T., Sekita K., Muso E., Tochino Y., Ida T., Kuzuya H. Prevention of type I diabetes in nonobese diabetic mice by allogenic bone marrow transplantation. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7743–7747. doi: 10.1073/pnas.82.22.7743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kanazawa Y., Komeda K., Sato S., Mori S., Akanuma K., Takaku F. Non-obese-diabetic mice: immune mechanisms of pancreatic beta-cell destruction. Diabetologia. 1984 Jul;27 (Suppl):113–115. doi: 10.1007/BF00275663. [DOI] [PubMed] [Google Scholar]
  13. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Larhammar D., Hammerling U., Denaro M., Lund T., Flavell R. A., Rask L., Peterson P. A. Structure of the murine immune response I-A beta locus: sequence of the I-A beta gene and an adjacent beta-chain second domain exon. Cell. 1983 Aug;34(1):179–188. doi: 10.1016/0092-8674(83)90148-4. [DOI] [PubMed] [Google Scholar]
  15. Lindstrom J. Immunobiology of myasthenia gravis, experimental autoimmune myasthenia gravis, and Lambert-Eaton syndrome. Annu Rev Immunol. 1985;3:109–131. doi: 10.1146/annurev.iy.03.040185.000545. [DOI] [PubMed] [Google Scholar]
  16. Makino S., Kunimoto K., Muraoka Y., Mizushima Y., Katagiri K., Tochino Y. Breeding of a non-obese, diabetic strain of mice. Jikken Dobutsu. 1980 Jan;29(1):1–13. doi: 10.1538/expanim1978.29.1_1. [DOI] [PubMed] [Google Scholar]
  17. Malissen M., Hunkapiller T., Hood L. Nucleotide sequence of a light chain gene of the mouse I-A subregion: A beta d. Science. 1983 Aug 19;221(4612):750–754. doi: 10.1126/science.6410508. [DOI] [PubMed] [Google Scholar]
  18. Mengle-Gaw L., Conner S., McDevitt H. O., Fathman C. G. Gene conversion between murine class II major histocompatibility complex loci. Functional and molecular evidence from the bm 12 mutant. J Exp Med. 1984 Oct 1;160(4):1184–1194. doi: 10.1084/jem.160.4.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mengle-Gaw L., McDevitt H. O. Isolation and characterization of a cDNA clone for the murine I-E beta polypeptide chain. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7621–7625. doi: 10.1073/pnas.80.24.7621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mori Y., Suko M., Okudaira H., Matsuba I., Tsuruoka A., Sasaki A., Yokoyama H., Tanase T., Shida T., Nishimura M. Preventive effects of cyclosporin on diabetes in NOD mice. Diabetologia. 1986 Apr;29(4):244–247. doi: 10.1007/BF00454884. [DOI] [PubMed] [Google Scholar]
  21. Nepom B. S., Palmer J., Kim S. J., Hansen J. A., Holbeck S. L., Nepom G. T. Specific genomic markers for the HLA-DQ subregion discriminate between DR4+ insulin-dependent diabetes mellitus and DR4+ seropositive juvenile rheumatoid arthritis. J Exp Med. 1986 Jul 1;164(1):345–350. doi: 10.1084/jem.164.1.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  23. Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
  24. Pierres M., Devaux C., Dosseto M., Marchetto S. Clonal analysis of B- and T-cell responses to Ia antigens. I. Topology of epitope regions on I-Ak and I-Ek molecules analyzed with 35 monoclonal alloantibodies. Immunogenetics. 1981 Dec;14(6):481–495. doi: 10.1007/BF00350120. [DOI] [PubMed] [Google Scholar]
  25. Saito H., Maki R. A., Clayton L. K., Tonegawa S. Complete primary structures of the E beta chain and gene of the mouse major histocompatibility complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5520–5524. doi: 10.1073/pnas.80.18.5520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shiroishi T., Sagai T., Moriwaki K. A new wild-derived H-2 haplotype enhancing K-IA recombination. Nature. 1982 Nov 25;300(5890):370–372. doi: 10.1038/300370a0. [DOI] [PubMed] [Google Scholar]
  28. Steinmetz M., Minard K., Horvath S., McNicholas J., Srelinger J., Wake C., Long E., Mach B., Hood L. A molecular map of the immune response region from the major histocompatibility complex of the mouse. Nature. 1982 Nov 4;300(5887):35–42. doi: 10.1038/300035a0. [DOI] [PubMed] [Google Scholar]
  29. Steinmetz M., Stephan D., Fischer Lindahl K. Gene organization and recombinational hotspots in the murine major histocompatibility complex. Cell. 1986 Mar 28;44(6):895–904. doi: 10.1016/0092-8674(86)90012-7. [DOI] [PubMed] [Google Scholar]
  30. Symington F. W., Sprent J. A monoclonal antibody detecting an Ia specificity mapping in the I-A or I-E subregion. Immunogenetics. 1981;14(1-2):53–61. doi: 10.1007/BF00344299. [DOI] [PubMed] [Google Scholar]
  31. Tiemeier D. C., Tilghman S. M., Leder P. Purification and cloning of a mouse ribosomal gene fragment in coliphage lambda. Gene. 1977;2(3-4):173–191. doi: 10.1016/0378-1119(77)90016-6. [DOI] [PubMed] [Google Scholar]

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