Skip to main content

Advertisement

SpringerLink
Log in

A Thy-1 − mutant defining a gene acting in trans position to regulate cell-surface Thy-1 glycoprotein expression and Thy-1 messenger RNA content

  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The Thy-1 glycoprotein is a differentiation antigen which exhibits tissue-specific regulation. A mutant of a Thy-1.1+ T-cell lymphoma has been isolated which does not express Thy-1 glycoprotein on the cell surface and does not accumulate Thy-1 mRNA in the cytoplasm. Hybrids between the mutant and a Thy-1.2+ T-cell lymphoma express 20–30-fold lower levels of Thy-1 glycoprotein on their cell surface compared to wild-type T-cell lymphomas, and they have correspondingly low levels of cytoplasmic Thy-1 mRNA. A revertant of one hybrid was isolated which expressed wild-type levels of both Thy-1 alleles on its surface and contained correspondingly increased levels of Thy-1 mRNA. A Thy-1+ revertant of the Thy-1 − mutant was isolated by cell sorting. A second generation Thy-1 − mutant could be isolated from this revertant which also did not accumulate Thy-1 mRNA and which behaved in a way similar to the first generation mutant when hybridized to a Thy-1.2+ lymphoma. No changes in the structure or copy number of the Thy-1 structural gene could be detected in this series of mutants and revertants. These properties are consistent with a mutation in one (or more) gene(s) which acts in trans position to regulate Thy-1 glycoprotein expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Accolla, R., Carra, G., and Guardiola, J.: Reactivation by a trans-acting-factor of human major histocompatibility complex la gene expression in interspecies hybrids between an Ia-negative human B-cell variant and an Ia-positive mouse B-cell lymphoma. Proc. Natl. Acad. Sci. U.S.A. 82: 5145–5149, 1985a

    Google Scholar 

  • Accolla, R., Scarpellino, L., Carra, G., and Guardiola, J.: Trans-acting elements operating across species barriers positively regulate expression of major histocompatibility complex class I genes. J. Exp. Med. 162: 1117–1133, 1985b

    Google Scholar 

  • Acton, R., Morris, R., and Williams, A.: Estimation of the amount and tissue distribution of rat Thy 1.1 antigen. Eur. J. Immunol. 4: 598–602, 1974

    Google Scholar 

  • Baldacci, P., Pozo, F., Gisselbrecht, S., and Kourilsky, P.: Altered transcription of genes coding for class I histocompatibility antigens in murine tumor cells. J. Exp. Med. 158: 1294–1306, 1983

    Google Scholar 

  • Berns, A., Lai, M., Bosselman, R., McKennett, M., Bacheler, L., Fan, H., Maandag, E., Patten, H., and Verma, I.: Molecular cloning of unintegrated and a portion of integrated Moloney murine leukemia viral DNA in bacteriophage lambda. J. Virol. 36: 259–263, 1980

    Google Scholar 

  • Croce, C., Linnenbach, A., Huebner, K., Parties, J., Margulies, D., Apella, E., and Seidman, J.: Control of expression of histocompatibility antigens (H-2) and β-2-microglobulin in F9 teratocarcinoma cells. Proc. Natl. Acad. Sci. U.S.A. 78: 5754–5758, 1981

    Google Scholar 

  • de Preval, C., Lisowski-Grospierre, B., Loche, M., Griscelli, C., and Mach, B.: A trans-acting class II regulatory gene unlinked to the MHC controls expression of HLA class II genes. Nature 318: 291–293, 1985

    Google Scholar 

  • Deschatrette, J., Fougere-Deschatrette, Corcos, L., and Schimke, R.: Expression of the mouse serum albumin gene introduced into differentiated and dedifferentiated rat hepatoma cells. Proc. Natl. Acad. Sci. U.S.A. 82: 765–769, 1985

    Google Scholar 

  • Evans, G., Ingraham, H., Lewis, K., Cunningham, K., Seki, T., Moriuchi, T., Chang, H., Silver, J., and Hyman, R.: Expression of the Thy-1 glycoprotein gene by DNA-mediated gene transfer. Proc. Natl. Acad. Sci. U.S.A. 81: 5532–5536, 1984

    Google Scholar 

  • Giguere, V., Isobe, K., and Grosveld, F.: Structure of the murine Thy-1 gene. EMBO J. 4: 2017–2024, 1985

    Google Scholar 

  • Gladstone, P. and Pious, D.: Identification of a trans-acting function regulating HLA-DR expression in a DR-negative B-cell variant. Somatic Cell Genet. 6: 285–298, 1980

    Google Scholar 

  • Greenberg, R., Mathieson, B., Campbell, P., and Zatz, M.: Multiple occurrence of spontaneous AKR/J lymphomas with T and B cell characteristics. J. Immunol. 118: 1181–1190, 1977

    Google Scholar 

  • Hansen, J.: Use of solubilizable acrylamide disulfide gels for isolation of DNA fragments suitable for sequence analysis. Anal. Biochem. 116: 146–151, 1981

    Google Scholar 

  • Horibata, K. and Harris, A.: Mouse myelomas and lymphomas in culture. Exp. Cell. Res. 60: 61–77, 1970

    Google Scholar 

  • Howell, D., Kostyu, D., Ting, J., and Cresswell, P.: Expression of class I histocompatibility antigens on human T-B lymphoblast hybrids. Somatic Cell Mol. Genet. 10: 217–224, 1984

    Google Scholar 

  • Hyman, R.: Cell-surface-antigen mutants of haematopoietic cells. Tools to study differentiation, biosynthesis, and function. Biochem. J. 225: 27–40, 1985

    Google Scholar 

  • Hyman, R. and Cunningham, K.: Regulation of Thy-1 and Pgp-1 glycoproteins in hybrids between T-cell lymphomas and Abelson-leukemia-virus-induced lymphomas. Immunogenetics 20: 677–691, 1984

    Google Scholar 

  • Hyman, R. and Stallings, V.: Evidence for a gene extinguishing cell-surface expression of the Thy-1 antigen. Immunogenetics 6: 447–458, 1978

    Google Scholar 

  • Hyman, R., Cunningham, K., and Stallings, V.: Evidence for a genetic basis for the class A Thy-1− defect. Immunogenetics 10: 261–271, 1980

    Google Scholar 

  • Hyman, R., Cunningham, K., and Stallings, V.: Effect of gene dosage on cell-surface expression of Thy-1 antigen in somatic cell hybrids between Thy-1−-Abelson-leukemia-virus-induced lym phomas and Thy-1+ mouse lymphomas. Immunogenetics 12: 381–395, 1981

    Google Scholar 

  • Hyman, R., Trowbridge, I., Stallings, V., and Trotter, J.: Revertant expressing a structural variant of T200 glycoprotein. Immunogenetics 15: 413–420, 1982

    Google Scholar 

  • Ingraham, H., Lawless, G., and Evans, G.: The mouse Thy-1.2 glycoprotein gene: Complete sequence and identification of an unusual promoter. J. Immunol. 136: 1482–1489, 1986

    Google Scholar 

  • Kawata, M., Parties, J., and Herzenberg, L.: Transcriptional control of HLA-A, B, C antigen in human placental cytotrophoblast isolated using trophoblast and HLA-specific monoclonal anti bodies and the fluorescence-activated cell sorter. J. Exp. Med. 160: 633–651, 1984

    Google Scholar 

  • Killary, A. and Fournier, R.: A genetic analysis of extinction: Transdominant loci regulate expression of liver-specific traits in hepatoma hybrid cells. Cell 38: 523–534, 1984

    Google Scholar 

  • Lesley, J., Hyman, R., Schulte, R., and Trotter, J.: Expression of transferrin receptor on murine hematopoietic progenitors. Cell. Immunol. 83: 14–25, 1984

    Google Scholar 

  • Levine, F. and Pious, D.: Revertants from the HLA class II regulatory mutant 6.1.6: Implications for the regulation of Ia gene expression. J. Immunol. 132: 959–962, 1984

    Google Scholar 

  • Morello, D., Daniel, F., Baldacci, P., Cayre, Y., Gachelin, G., and Kourilsky, P.: Absence of significant H-2 and β-2 microglobulin mRNA expression by mouse embryonal carcinoma cells. Nature 296: 260–262, 1982

    Google Scholar 

  • Moriuchi, T., Chang, H.-C., Denome, R., and Silver, J.: Thy-1 cDNA sequence suggests a novel regulatory mechanism. Nature 301: 80–82, 1983

    Google Scholar 

  • Ott, M.-O., Sperling, L., Herbomel, P., Yaniv, M., and Weiss, M.: Tissue-specific expression is conferred by a sequence from the 5′ end of the rat albumin gene. EMBO J. 3: 2505–2510, 1984

    Google Scholar 

  • Owen, J. and Raff, M.: Studies on the differentiation of thymus-derived lymphocytes. J. Exp. Med. 132: 1216–1232, 1970

    Google Scholar 

  • Papayannopoulou, T., Lindsley, D., Kurachi, S., Lewison, K., Henenway, T., Melis, M., Agagnon, N., and Najfeld, V.: Adult and fetal human globin genes are expressed following chromosomal transfer into MEL cells. Proc. Natl. Acad. Sci. U.S.A. 82: 780–784, 1985

    Google Scholar 

  • Peterson, T., Killary, A., and Fournier, R.: Chromosomal assignment and trans regulation of the tyrosine aminotransferase structural gene in hepatoma hybrid cells. Mol. Cell. Biol. 5: 2491–2494, 1985

    Google Scholar 

  • Reif, A. and Allen, J.: The AKR thymic antigen and its distribution in leukemias and nervous tissues. J. Exp. Med. 120: 413–433, 1964

    Google Scholar 

  • Salter, R. D., Howell, D. N., and Cresswell, P.: Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids. Immunogenetics 21: 235–246, 1985a

    Google Scholar 

  • Salter, R., Alexander, J., Levine, F., Pious, D., and Cresswell, P.: Evidence for two trans-acting genes regulating HLA class II antigen expression. J. Immunol. 135: 4235–4238, 1985b

    Google Scholar 

  • Salzman, G., Wilkins, S., and Whitfill, J.: Modular computer programs for flow cytometry and sorting: The LACEL system. Cytometry 1: 325–336, 1981

    Google Scholar 

  • Trowbridge, L., Hyman, R., and Mazauskas, C.: The synthesis and properties of T25 glycoprotein in Thy-l-negative mutant lymphoma cells. Cell 14: 21–32, 1978

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Biology Laboratory, The Salk Institute for Biological Studies, Box 85800, 92138, San Diego, California

    Robert Hyman & Kristie Cunningham

Authors
  1. Robert Hyman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristie Cunningham
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hyman, R., Cunningham, K. A Thy-1 − mutant defining a gene acting in trans position to regulate cell-surface Thy-1 glycoprotein expression and Thy-1 messenger RNA content. Immunogenetics 23, 312–321 (1986). https://doi.org/10.1007/BF00398795

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00398795

Keywords

Search

Navigation