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.
Similar content being viewed by others
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.
Bailey, D.W. (1975). Genetics of histocompatibility in mice I. New loci and congenic lines. Immunogenetics 2, 249–256.
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.
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.
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.
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.
Davis, A.P., Roopenian, D.C. (1990). Complexity at the mouse minor histocompatibility locus H-4. Immunogenetics 31, 7–12.
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.
Falk, K., Rötzschke, O., Rammensee, H.G. (1990). Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature 348, 248–251.
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.
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.
Gasser, D.L. (1976a). Genetic studies on the H-3 region of mice and implications for polymorphism of histocompatibility loci. Immunogenetics 3, 271–276.
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.
Graff, R.J., Brown, D., Snell, G.D. (1978). The alleles of the H-13 locus. Immunogenetics 7, 413–423.
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.
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.
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.
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.
Hillyard, A.L., Doolittle, D.P., Davisson, M.T., Roderick, T.H. (1992). Locus map of the mouse. Mouse Genome 90, 8–21.
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.
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.
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.
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.
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.
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.
Neumann, P.E. (1992). Does sex of the offspring influence transmission ratio? Genetics 130, 685–686.
Perreault, C., Decary, F., Brochu, S., Gyger, M., Belanger, R., Roy, D. (1990). Minor histocompatibility antigens. Blood 76, 1269–1280.
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.
Rammensee, H.-G., Klein, J. (1983). Complexity of the Histocompatibility-3 region in the mouse. J. Immunol. 130, 2926–2929.
Roopenian, D.C. (1992). What are minor histocompatibility loci? A new look at an old question. Immunol. Today 13, 7–10.
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.
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.
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.
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.
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).
Silver, L.M. (1985). Mouse t-haplotypes. Annu. Rev. Genet. 19, 179–208.
Siracusa, L.D., Abbott, C.M. (1992). Mouse Chromosome 2. Mammalian Genome 3, (Suppl): S20-S43.
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.
Snell, G.D. (1958). Histocompatibility genes of the mouse. II. Production and analysis of isogenic resistant lines. J. Natl. Cancer Inst. 21, 843–877.
Snell, G.D., Bunker, H.P. (1960). Histocompatibility genes of mice. Transplantation 2, 743–751.
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.
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.
Wallney, H.J., Rammensee, H.G. (1990). Identification of classical minor histocompatibility antigen as cell derived peptide. Nature 343, 275–278.
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.
Woodland, D.L., Blackman, M.A. (1992). Retroviral super-antigens and T cells. Int. Rev. Immunol. 8, 311–325.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00364787