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High-resolution mapping of a minor histocompatibility antigen gene on mouse chromosome 2

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Abstract

Minor histocompatibility (H) loci are significant tissue transplantation barriers but are poorly understood at the genetic and molecular level. We describe the construction of a high-resolution genetic map that positions a class II MHC-restricted minor H antigen locus and orders 12 other genes and genetic markers within the we-un interval of mouse Chromosome (Chr) 2. An intersubspecific backcross between 10.UW/Sn-H-3 b and CAST/Ei, an inbred stock of Mus musculus castaneus, was used for this purpose. A total of 1168 backcross mice were generated, and 71 we-un recombinants were identified. Significant compression of the genetic map in males versus females and transmission distortion of CAST-derived we, un, and Aw genes were observed. Monoclonal T cell lines specific for two minor H alloantigens, Hd-1a and Hd2a, encoded by gene(s) that map to the we-un interval were used to antigen type the backcross mice. The results suggest the Hd-1a and Hd-2a antigens are most likely encoded by a single gene, now referred to as H-3b. The determined gene order is we-0.09±0.09-Itp-0.62±0.23-D2Mit77-0.26±0.15[Evi-4, Pcna, Prn-p]-0.26±0.15-Scg-1-0.44±0.19-[Bmp2a, D2Mit70]-0.09±0.09-[D2Mit19, D2Mit46]-1.59±0.36-D2Mit28-0.97±0.28-D2Lerl-1.50±0.35-H-3b-0.26±0.15-un (% recombination±1 SE). Because the average resolution of the backcross is 0.09 cM, the backcross panel should facilitate the physical mapping and molecular identification of a number of genes in this chromosome region.

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References

  • Abbott, C., Pilz, A., Moseley, H. Peters, J. (1992). The gene for proliferating cell nuclear antigen (Pcna) maps to mouse Chromosome 2. Mammalian Genome 3, 286–289.

    Google Scholar 

  • Bailey, D.W. (1975). Genetics of histocompatibility in mice I. New loci and congenic lines. Immunogenetics 2, 249–256.

    Google Scholar 

  • Balling, R., Deutsch, U., Gruss, P. (1988). Undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax-1. Cell 55, 531–535.

    Google Scholar 

  • Carlson, G.A., Goodman, P.A., Lovett, M., Taylor, B.A., Marshall, S.T., Peterson-Torchia, M., Westaway, D., Prusiner, S.B. (1988). Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time. Mol. Cell. Biol. 8, 5528–5540.

    Google Scholar 

  • Carlson, G.A., Ebeling, C., Torchia, M., Westaway, D., Prusiner, S.B. (1993). Delimiting the location of the scrapie prion incubation time gene on Chromosome 2 of the mouse. Genetics, in press.

  • Ceci, J.D., Siracusa, L.D., Jenkins, N.A., Copeland, N.G. (1989). A molecular genetic linkage map of mouse Chromosome 4 including localization of several proto-oncogenes. Genomics 5, 699–709.

    Google Scholar 

  • Copeland, N.G., Gilbert, D.J., Chretien, M., Seidah, N.G., Jenkins, N.A. (1992). Regional localization of three convertases, PC1 (Nec-1), PC2 (Nec-2), and Furin (Fur), on mouse chromosomes. Genomics 13, 1356–1358.

    Google Scholar 

  • Davis, A.P., Roopenian, D.C. (1990). Complexity at the mouse minor histocompatibility locus H-4. Immunogenetics 31, 7–12.

    Google Scholar 

  • Dietrich, W., Katz, H., Lincoln, S.E., Shin, H.-S., Friedman, J., Dracopi, N.C., Lander, E.S. (1992). A genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131, 423–447.

    Google Scholar 

  • Falk, K., Rötzschke, O., Rammensee, H.G. (1990). Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature 348, 248–251.

    Google Scholar 

  • Falk, K., Rötzschke, O., Stevanovic, S., Jung, G., Rammansee, H.-G. (1991). Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351, 290–296.

    Google Scholar 

  • Frankel, W.N., Stoye, J.P., Taylor, B.A., Coffin, J.M. (1990). A linkage map of endogenous murine leukemia proviruses. Genetics 124, 221–236.

    Google Scholar 

  • Gasser, D.L. (1976a). Genetic studies on the H-3 region of mice and implications for polymorphism of histocompatibility loci. Immunogenetics 3, 271–276.

    Google Scholar 

  • Gasser, D.L. (1976b). H-3-linked unresponsiveness to Ea-1 and H-13 antigens. In The Role of the Major Histocompatibility Complex in Immune Responses, D.H. Katz, B. Benacerraf, eds. (New York: Academic Press), pp. 289–295.

    Google Scholar 

  • Graff, R.J., Brown, D., Snell, G.D. (1978). The alleles of the H-13 locus. Immunogenetics 7, 413–423.

    Google Scholar 

  • Graff, R.J., Martin-Morgan, D., Kurtz, M.E. (1985). Allograft rejection-defined antigens of the B2m, H-3 region. J. Immunol. 135, 2842–2846.

    Google Scholar 

  • Graff, R.J., Kurtz, M.E., Paul, R., Martin, D., Roopenian, D.C. (1991). Additional mapping of mouse Chromosome 2 genes. Immunogenetics 33, 96–100.

    Google Scholar 

  • Green, M.C. (1981). Gene mapping. In The Mouse in Biomedical Research, H.L. Foster, J.D. Small, J.D. Fox, eds. (New York: Academic Press), pp. 105–117.

    Google Scholar 

  • Hess, E.J., Jinnah, H.A., Kozak, C.A., Wilson, M.C. (1992). Spontaneous locomotor hyperactivity in a mouse mutant with a deletion including the Snap gene on Chromosome 2. J. Neurosci. 12, 2865–2874.

    Google Scholar 

  • Hillyard, A.L., Doolittle, D.P., Davisson, M.T., Roderick, T.H. (1992). Locus map of the mouse. Mouse Genome 90, 8–21.

    Google Scholar 

  • Joseph, D.R., Sullivan, P.M., Wang, Y.-M., Kozak, C., Fenstermacher, D.A., Behrendsen, M.E., Zahnow, C.A. (1990). Characterization and expression of the complementary DNA encoding rat histidine decarboxylase. Proc. Natl. Acad. Sci. USA 87, 733–737.

    Google Scholar 

  • Justice, M.J., Siracusa, L.D., Gilbert, D.J., Heisterkamp, N., Groffen, J., Chada, K., Silan, C.M., Copeland, N.G., Jenkins, N.A.. (1990). A genetic linkage map of mouse Chromosome 10: localization of eighteen molecular markers using a single interspecific backcross. Genetics 125, 855–866.

    Google Scholar 

  • Kurtz, M.E., Graff, R.J., Adelman, A., Martin-Morgan, D., Click, R.E. (1985). CTL and serologically defined antigens of B2m, H-3 region. J. Immunol. 135, 2847–2852.

    Google Scholar 

  • Le Roy, H., Simon-Chazottes, D., Montagutelli, X., Guénet, J.-L. (1992). A set of anomymous DNA clones as markers for mouse gene mapping. Mammalian Genome 3, 244–246.

    Google Scholar 

  • Love, J.M., Knight, A.M., McAleer, M.A., Todd, J.A. (1990). Towards construction of a high resolution map of the mouse genome using PCR-analysed microsatellites. Nucleic Acids Res. 18, 4123–4130.

    Google Scholar 

  • Loveland, B.E., Fischer Lindahl, K. (1991). The definition and expression of minor histocompatibility antigens. In Antigen Processing and recognition, J. McCluskey, ed. (Boca Raton, Fla.: CRC Press), pp. 173–192.

    Google Scholar 

  • Neumann, P.E. (1992). Does sex of the offspring influence transmission ratio? Genetics 130, 685–686.

    Google Scholar 

  • Perreault, C., Decary, F., Brochu, S., Gyger, M., Belanger, R., Roy, D. (1990). Minor histocompatibility antigens. Blood 76, 1269–1280.

    Google Scholar 

  • Prochazka, M., Gold, D.P., Castano, L., Eisenbarth, G.S., Paigen, B., Leiter, E.H., (1991). Mapping of secretogranin 1 (Scg-1) to Chr 2, and carboxypeptidase H (Cph-1) to Chr 8. Mouse Genome 89, 280.

    Google Scholar 

  • Rammensee, H.-G., Klein, J. (1983). Complexity of the Histocompatibility-3 region in the mouse. J. Immunol. 130, 2926–2929.

    Google Scholar 

  • Roopenian, D.C. (1992). What are minor histocompatibility loci? A new look at an old question. Immunol. Today 13, 7–10.

    Google Scholar 

  • Roopenian, D.C., Click, R.E. (1980). A new cytotoxic lymphocytedefined antigen coded for by a gene closely linked to the H-3 locus. Immunogenetics 10, 333–334.

    Google Scholar 

  • Roopenian, D.C., Davis, A.P. (1989). Responses against antigens encoded by the H-3 histocompatibility locus: antigens stimulating class I MHC- and class II MHC-restricted T cells are encoded by separate genes. Immunogenetics 30, 335–343.

    Google Scholar 

  • Roopenian, D.C., Orosz, C.G., Bach, F.H.J.I. (1984). Responses against single minor histocompatibility antigens. II. Analysis of cloned helper T cells. J. Immunol. 132, 1080–1084.

    Google Scholar 

  • Roopenian, D.C., Christianson, G.J., Davis, A.P., Zuberi, A.R., Mobraaten, L.E. (1993a). The genetic origin of minor histocompatibility antigens. Immunogenetics 38, 131–140.

    Google Scholar 

  • Roopenian, D.C., Davis, A.P., Christianson, G.J., Mobraaten, L.E. (1993b). The functional organization of minor histocompatibility loci. J. Immunol., in press.

  • Sambrook, J., Fritsch, E.F., Maniatis, T. (1989). In Molecular Cloning, a Laboratory Manual. (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press).

    Google Scholar 

  • Silver, L.M. (1985). Mouse t-haplotypes. Annu. Rev. Genet. 19, 179–208.

    Google Scholar 

  • Siracusa, L.D., Abbott, C.M. (1992). Mouse Chromosome 2. Mammalian Genome 3, (Suppl): S20-S43.

    Google Scholar 

  • Siracusa, L.D., Alvord, W.G., Bickmore, W.A., Jenkins, N.A., Copeland, N.G. (1991). Interspecific backcross mice show sexspecific differences in allelic inheritance. Genetics 128, 813–821.

    Google Scholar 

  • Snell, G.D. (1958). Histocompatibility genes of the mouse. II. Production and analysis of isogenic resistant lines. J. Natl. Cancer Inst. 21, 843–877.

    Google Scholar 

  • Snell, G.D., Bunker, H.P. (1960). Histocompatibility genes of mice. Transplantation 2, 743–751.

    Google Scholar 

  • Spence, S.E., Gilbert, D.J., Harris, B.S., Davisson, M.T., Copel N.G., Jenkins, N.A. (1992). Genetic localization of Hao-1, blind-sterile (bs), and Emv-13 on mouse Chromosome 2. Genomics 12, 403–404.

    Google Scholar 

  • Taylor, B.A., Walls, D.M., Wimsatt, M.J. (1987). Localization of the inosine triphosphatase locus (Itp) on Chromosome 2 of the mouse. Biochem. Genet. 25, 267–274.

    Google Scholar 

  • Wallney, H.J., Rammensee, H.G. (1990). Identification of classical minor histocompatibility antigen as cell derived peptide. Nature 343, 275–278.

    Google Scholar 

  • Watanabe, T., Miyashita, N., Nishimura, M., Saitou, N., Hayashi, Y., Moriwaki, K. (1989). Evolutionary relationships between laboratory mice and subspecies of Mus musculus based on the restriction fragment length variants of the chymotrypsin gene at the Prit-2 locus. Biochem. Genet. 27, 119–130.

    Google Scholar 

  • Woodland, D.L., Blackman, M.A. (1992). Retroviral super-antigens and T cells. Int. Rev. Immunol. 8, 311–325.

    Google Scholar 

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  1. The Jackson Laboratory, 04609, Bar Harbor, Maine, USA

    Aamir R. Zuberi & Derry C. Roopenian

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  1. Aamir R. Zuberi
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  2. Derry C. Roopenian
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Zuberi, A.R., Roopenian, D.C. High-resolution mapping of a minor histocompatibility antigen gene on mouse chromosome 2. Mammalian Genome 4, 516–522 (1993). https://doi.org/10.1007/BF00364787

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