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The Mouse Rhl1 and Rhag Genes: Sequence, Organization, Expression, and Chromosomal Mapping

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Abstract

To seek an alternative model for studies of theRh protein complex, we isolated by homology cloning andcharacterized the mouse Rhced and Rhaggenes, which are homologous to the human RH andRHAG genes,respectively. Rhced encodes a glycoprotein of418 amino acids which occurs as a composite of human RhDand RhCE with 60% identity and 74% similarity. Rhagencodes a glycoprotein of 438 amino acids thatshares 79% identity and 87% similarity to humanRh50. However, Rhag has an elongated C terminus and fourN-glycosylation sites clustered on exoloop 1. Hydropathyplots suggest that Rhl1 and Rhag each spanthe lipid bilayer 12 times, with N and Ctermini facing the cytoplasm. Rhced and Rhag are bothspecified by 10 exons and bear a similar exon/intronstructure, but their major transcription start sites aremapped at –17A and –27A. Northernanalysis revealed coexpression of Rhced and Rhag from11-day embryos throughout adult life in erythroidtissues. Southern blotting and linkage analysis showedthat Rhced and Rhag are single-copygenes localized to chromosomes 4 and 17, respectively;they are paralogous to one another but orthologous tohuman RH and RHAG. The resultstogether predate the occurrence and signifya conserved function of the erythroid-specificRh membrane structures.

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REFERENCES

  • Agre, P., and Cartron, J.-P. (1991). Molecular biology of Rh antigens. Blood 78:551.

    Google Scholar 

  • Anstee, D. J., and Tanner, M. J. A. (1993). Biochemical aspects of the blood group Rh (rhesus) antigens. Bailliere Clin. Haematol. 6:401.

    Google Scholar 

  • Arce, M. A., Thompson, E. S., Wagner, S., Coyne, K. E., Ferdman, B. A., and Lublin, D. M. (1993). Molecular cloning of RhD cDNA derived from a gene present in RhD-positive, but not RhD-negative individuals. Blood 82:651.

    Google Scholar 

  • Avent, N. D., Ridgwell, K., Tanner, M. J. A., and Anstee, D. J. (1990). cDNA cloning of a 30kDa erythrocyte membrane protein associated with Rh (Rhesus)-blood-group-antigen expression. Biochem. J. 271:821.

    Google Scholar 

  • Cartron, J.-P., and Agre, P. (1995). Rh blood groups and Rh-deficiency syndrome. Blood Cell Biochem. 8:199.

    Google Scholar 

  • Cherif-Zahar, B., Bloy, C., Le Van Kim, C., Blanchard, D., Bailly, P., Hermand, P., Salmon, C., Cartron, J.-P., and Colin, Y. (1990). Molecular cloning and protein structure of a human blood group Rh polypeptide. Proc. Natl. Acad. Sci. USA 87:6243.

    Google Scholar 

  • Cherif-Zahar, B., Le Van Kim, C., Rouillac, C., Raynal, V., Cartron, J.-P., and Colin, Y. (1994). Organization of the gene (RHCE) encoding the human blood group RhCcEe antigens and characterization of the promoter region. Genomics 19:68.

    Google Scholar 

  • Cherif-Zahar, B., Raynal, V., Gane, P., Mattei, M.-G., Bailly, P., Gibbs, B., Colin, Y., and Cartron, J.-P. (1996). Candidate gene acting as a suppressor of the RH locus in most cases of Rh-deficiency. Nature Genet. 12:168.

    Google Scholar 

  • Cherif-Zahar, B., Matassi, G., Raynal, V., Gane, P., Mempel, W., Perez, C., and Cartron, J.-P. (1998). Molecular defects of the RHCE gene in Rh-deficient individuals of the amorph type. Blood 92:639.

    Google Scholar 

  • DeBry, R. W., and Seldin, M. F. (1996). Human/mouse homology relationships. Genomics 33:337.

    Google Scholar 

  • Eyers, S.A. C., Ridgwell, K., Mawby, W. J., and Tanner, M. J. A. (1994). Topology and organization of the human Rh (Rhesus) blood group-related polypeptides. J. Biol. Chem. 269:6417.

    Google Scholar 

  • Gilbert, S. F. (1988). Developmental Biology, 2nd ed., Sinauer Associates, Sunderland, MA.

    Google Scholar 

  • Henikoff, S., Greene, E. A., Pietrokovski, S., Bork, P., Attwood, T. K., and Hood, L. (1997). Gene families: The taxonomy of protein paralogs and chimeras. Science 278:609.

    Google Scholar 

  • Huang, C.-H. (1996). Alteration of RH gene structure and expression in dCCee and DCW-red blood cells: Phenotypic homozygosity versus genotypic heterozygosity. Blood 88:2326.

    Google Scholar 

  • Huang, C.-H. (1997). Molecular insights into the Rh protein family and associated antigens. Curr. Opin. Hematol. 4:94.

    Google Scholar 

  • Huang, C.-H. (1998). The human Rh50 glycoprotein gene: Structural organization and associated splicing defect resulting in Rhnull disease. J. Biol. Chem. 273:2207.

    Google Scholar 

  • Huang, C.-H., Chen, Y., Reid, M. E., and Seidl, C. (1998a). Rhnull disease: the amorph type results from a novel double mutation in RhCe gene on D-negative background. Blood 92:664.

    Google Scholar 

  • Huang, C.-H., Liu, Z., Cheng, G. J., and Chen, Y. (1998b). Rh50 glycoprotein gene and Rhnull disease: A silent splice donor is trans to a Gly279 →Glu missense mutation in the conserved transmembrane segment. Blood 92:1776.

    Google Scholar 

  • Hyland, C.A., Cherif-Zahar, B., Cowley, N., Raynal, V., Parks, J., Saul, A., and Cartron, J.-P. (1998). A novel single missense mutation identified along the RH50 gene in a composite heterozygous Rhnull blood donor of the regulator type. Blood 91:1458.

    Google Scholar 

  • Iwamoto, S., Omi, T., Yamasaki, M., Okuda, H., Kawano, M., and Kajii, E. (1998). Identification of 5′ flanking sequence of RH50 gene and the core region for erythroid-specific expression. Biochem. Biophys. Res. Commun. 243:233.

    Google Scholar 

  • Kitano, T., Sumiyama, K., Shiroishi, T., and Saitou, N. (1998). Converved evolution of the Rh50 gene compared to its homologous Rh blood group gene. Biochem. Biophys. Res. Commun. 249:78.

    Google Scholar 

  • Kyte, J., and Doolittle, F. (1982). A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157:105.

    Google Scholar 

  • Le Van Kim, C., Mouro, I., Cherif-Zahar, B., Raynal, V., Cherrier, C., Cartron, J.-P., and Colin, Y. (1992). Molecular cloning and primary structure of the human blood group RhD polypeptide. Proc. Natl. Acad. Sci. USA 89:10925.

    Google Scholar 

  • Marini, A.-M., Urrestarazu, A., Beauwens, R., and Andre, B. (1997). The Rh (Rhesus) blood group polypeptides are related to NH4 + transporters. Trends Biochem. Sci. 22:460.

    Google Scholar 

  • Matassi, G., Cherif-Zahar, B., Raynal, V., Rouger, P., and Catron, J.-P. (1998). Organization of the human RH50A gene and evolution of base composition of the RH gene family. Genomics 47:286.

    Google Scholar 

  • Mollison, P. L., Engelfreit, C. P., and Contreras, M. (1993). Blood Transfusion in Clinical Medicine, Blackwell, Oxford.

    Google Scholar 

  • Nash, R., and Shojania, A.M. (1987). Hematological aspects of Rh deficiency syndrome: A case report and a review of the literature. Am. J. Hematol. 24:267.

    Google Scholar 

  • Ridgwell, K., Spurr, N. K., Laguda, B., MacGeoch, C., Avent, N. D., and Tanner, M. J. A. (1992). Isolation of cDNA clones for a 50 kDa glycoprotein of the human erythrocyte membrane associated with Rh (Rhesus) blood group antigen expression. Biochem. J. 287:223.

    Google Scholar 

  • Rowe, L. B., Nadeau, J. H., Turner, R., Franke, W. N., Letts, V.A., Eppig, J. T., Ko, M. S. H., Thurston, S. J., and Birkenmeier, E. H. (1994). Maps from two interspecific backcross DNA panels available as a community genetic mapping resource. Mammal. Genome 5:253.

    Google Scholar 

  • Sambrook, J., Fristch, E. F., and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

    Google Scholar 

  • Schroit, A. J., Bloy, C., Conner, J., and Cartron, J.-P. (1990). Involvement of Rh blood group polypeptides in the maintenance of aminophopholipid asymmetry. Biochemistry 29:10303.

    Google Scholar 

  • Seack, J., Pancer, Z., Muller, I. M., and Muller, W. E. G. (1997). Molecular cloning and primary structure of a Rhesus (Rh)-like protein from the marine sponge Geodia cydonium. Immunogenetics 46:493.

    Google Scholar 

  • Shapiro, M. B., and Senapathy, P. (1987). RNA splice junctions of different classes of eukaryotes: Sequence statistics and functional implications in gene expression. Nucleic Acid Res. 15:7155.

    Google Scholar 

  • Smith, R. E., and Daleke, D. L. (1990). Phosphotidylserine transport in Rhnull erythrocytes. Blood 76:1021.

    Google Scholar 

  • Wilson, R., Ainscough, R., Anderson, K., Baynes, C., Berks, M., Bornfield, J., Burton, J., et al. (1994). 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature 368:32.

    Google Scholar 

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Liu, Z., Huang, CH. The Mouse Rhl1 and Rhag Genes: Sequence, Organization, Expression, and Chromosomal Mapping. Biochem Genet 37, 119–138 (1999). https://doi.org/10.1023/A:1018726303397

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  • DOI: https://doi.org/10.1023/A:1018726303397

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