Abstract
The mouse genome contains four functional J H genes, which encode immunoglobulin heavy chain joining segments. The J H gene cluster is located a few kilobases 5′ from the constant region genes (C genes) on chromosome 12. The polymerase chain reaction (PCR)-technique was used to amplify DNA stretches from mouse genome of approximately 1 340 nucleotides in length containing all four J H genes (Igh-J locus). PCR products were directly used as templates in Sanger's dideoxy-sequencing, and sequences were determined. Twelve inbred mouse strains belonging to ten different Igh-C haplotypes were studied. The strains were: BALB/c, C58/J, RIII, DBA/2, CE, RF, CBA, NZB/J, AKR, C57BL/10, SJL, and A/J. Five allelic forms of the Igh-J locus were found among these strains. The A/J mouse has an allele (e) which differs from the BALB/c allele (a) by 15 nucleotides. C57BL and SJL have the allele (b) with eight differences from BALB/c. The CBA allele (j) has two differences, and the CE allele (f) has a single nucleotide difference compared with the BALB/c sequence. Based on the J H , variable (V) and constant (C) region sequences we conclude that independent reshuffling of V H ,J H , and C H gene clusters occurred during the evolution of Mus musculus.
Similar content being viewed by others
References
Berek, C.: The D segment defines the T15 idiotype: the immunoresponse of A/J mice to Pneumococcus pneumoniae. Eur J Immunol 14: 1043–1048, 1984
Brodeur, P. H. and Riblet, R.: The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred (Igh-V) genes comprise seven families of homologous genes. Eur J Immunol 14: 922–930, 1984
Clarke, S. H., Claflin, J. L., Potter, M., and Rudikoff, S.: Polymorphism in anti-phosphocholine antibodies reflecting evolution of immunoglobulin families. J Exp Med 157: 98–113,1983
Goldberg, G. I., Vanin, E. F., Zrolka, A. M., and Blattner, F. R.: Sequence of the gene for the constant region of the μ chain of BALB/c mouse immunoglobulin. Gene 15: 33–42, 1981
Gough, N. M. and Bernard, O.: Sequences of the joining region genes for immunoglobulin heavy chains and their role in generation of antibody diversity. Proc Natl Acad Sci USA 78: 509–513, 1981
Gyllenstein, U. B. and Erlich, H. A.: Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc Natl Acad Sci USA 85: 7652–7656, 1988
Kaartinen, M., Rocca-Serra, J., and Mäkelä, O.: Combinatorial association of V genes: one VH gene codes for three non-cross-reactive monoclonal antibodies each specific for a different antigen (phOxazolone, NP, or GAT). Mol Immunol 25: 859–865, 1988
Kaartinen, M., Solin, M.-L., and Mäkelä, O.: ‘Allelic’ forms of immunoglobulin V genes in different strains of mice. EMBO J 8: 1743–1748, 1989
Kaartinen, M., Solin, M.-L., and Mäkelä, O.: V genes of oxazolone antibodies in 10 strains of mice. Eur J Immunol 21: 2863–2869, 1991
Kawakami, T., Takahashi, N., and Honjo, T.: Complete nucleotide sequence of mouse immunoglobulin μ gene and comparison with other immunoglobulin heavy chain genes. Nucleic Acids Res 8: 3933–3945, 1980
Kim, S., Davis, M., Sinn, E., Patten, P., and Hood, L.: Antibody diversity: somatic hypermutation of rearranged V H genes. Cell 27: 573–581, 1981
Kofler, R., Perlmutter, R. M., Noonan, D. J., Dixon, F. J., and Theofilopoulos, A. N.: Ig heavy chain variable region gene complex of lupus mice exhibits normal restriction fragment length polymorphism. J Exp Med 162: 346–351, 1985
Kurosawa, Y. and Tonegawa, S.: Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments. J Exp Med 155: 201–218, 1982
Lebecque, S. G. and Gearhart, P. J.: Boundaries of somatic mutation in rearranged immunoglobulin genes: 5′ boundary is near the promoter, and 3′ boundary is ≈ 1 kb from V(D)J gene. J Exp Med 172: 1717–1727, 1990
Lieberman, R.: Genetics of IgCH (allotype) locus in the mouse. Springer Seminars in Immunopathol 1: 7–30, 1978
Livant, D., Blatt, C., and Hood, L.: One heavy chain variable region gene segment subfamily in the BALB/c mouse contains 500–1 000 or more members. Cell 47: 461–470, 1986
Maizels, N. and Bothwell, A.: The T-cell-independent immune response to the hapten NP uses a large repertoire of heavy chain genes. Cell 43: 715–720, 1985
Newell, N., Richards, J. E., Tucker, P. W., and Blattner, F. R.: J genes for heavy chain immunoglobulins of mouse. Science 209: 1128–1132, 1980
Ollo, R. and Rougeon, F.: Mouse immunoglobulin allotypes: post-duplication divergence of γ2a and γ2b chain genes. Nature 296: 761–763, 1982
Ollo, R. and Rougeon, F.: Gene conversion and polymorphism: Generation of mouse immunoglobulin γ2a chain alleles by differential gene conversion by γ2b chain gene. Cell 32: 515–523, 1983
Parsons, M., Herzenberg, L. A., Stall, A. M., and Herzenberg, L. A.: Mouse immunoglobulin allotypes. In D. M. Weir (ed.): Genetics and molecular immunology, Vol. 3, pp. 97.1–97.17, Blackwell Scientific Publications, Oxford, 1986
Rathbun, G., Berman, J., Yancopoulos, G., and Alt, F. W.: Organization and expression of the mammalian heavy-chain variable-region locus. In T. Honjo, F. W. Alt, and T. H. Rabbits (eds.): Immunoglobulin Genes, pp. 63–90, Academic Press, London, 1989
Sakano, H., Maki, R., Kurosawa, Y., Roeder, W., and Tonegawa, S.: Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature 286: 676–683, 1980
Sakano, H., Kurosawa, Y., Weigert, M., and Tonegawa, S.: Identification and nucleotide sequence of a diversity DNA segment (D) of immunoglobulin heavy-chain genes. Nature 290: 562–565, 1981
Sanger, F., Nicklen, S., and Coulson, A. R.: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977
Schreier, P. H., Bothwell, A. L. M., Mueller-Hill, B., and Baltimore, D.: Multiple differences between the nucleic acid sequences of the IgG2a and IgG2b alleles of the mouse. Proc Natl Acad Sci USA 78: 4495–4499, 1981
Schreier, P. H., Quester, S., and Bothwell, A.: Allotypic differences in murine μ genes. Nucleic Acids Res 14: 2381–2389, 1986
Shinkai, Y., Nakauchi, H., Honjo, T., and Okumura, K.: Mouse immunoglobulin allotypes: multiple differences between the nucleic acid sequences of the IgE a and IgE b alleles. Immunogenetics 27: 288–292, 1988
Sikder, S. K., Akolkar, P. N., Kaladas, P. M., Morrison, S. L., and Kabat, E. A.: Sequences of variable region of hybridoma antibodies to α(1→6) dextran in BALB/c and C57BL/6 mice. J Immunol 135: 4215–4221, 1985
Tabor, S. and Richardson, C. C.: DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci USA 84: 4767–4771, 1987
Trepicchio, W., Jr. and Barrett, K. J.: The Igh-V locus of MRL mice: restriction fragment length polymorphism in eleven strains of mice as determined with VH and D gene probes. J Immunol 134: 2734–2739, 1985
Wong, C., Dowling, C. E., Saiki, R. K., Higuchi, R. G., Erlich, H. A., and Kazazian, H. H., Jr.: Characterization of β-thalassemia mutations using direct genomic sequencing of amplified single copy DNA. Nature 330: 384–386, 1987
Wood, C. and Tonegawa, S.: Diversity and joining segments of mouse immunoglobulin heavy chain genes are closely linked and in the same orientation: Implications for the joining mechanism. Proc Natl Acad Sci USA 80: 3030–3034, 1983
Yamawaki-Kataoka, Y., Kataoka, T. Takahashi, N., Obata, M., and Honjo, T.: Complete nucleotide sequence of immunoglobulin γ2b chain gene cloned from newborn mouse DNA. Nature 283: 786–789, 1980
Author information
Authors and Affiliations
Additional information
The nucleotide sequence data reported in this paper have been submitted to the EMBL nucleotide sequence database and have been assigned the accession numbers X63146-X63175.
Rights and permissions
About this article
Cite this article
Solin, ML., Kaartinen, M. Allelic polymorphism of mouse Igh-J locus, which encodes immunoglobulin heavy chain joining (JH) segments. Immunogenetics 36, 306–313 (1992). https://doi.org/10.1007/BF00215659
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00215659