Infection of Developing Mouse Embryos with Murine Leukemia Virus: Tissue Specificity and Genetic Transmission of the Virus

  • Rudolf Jaenisch
  • Jessica Dausman
  • Virginia Cox
  • Hung Fan
Conference paper
Part of the Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 19)

Abstract

The tissue specificity of Moloney leukemia virus (M-MuLV) was studied by infecting mice at two different stages of development. Either newborn mice which can be considered as essentially fully differentiated animals were infected with M-MuLV or preimplantation mouse embryos were infected in vitro at the 4–8 cell stage, a stage of development before any differentiation has taken place. After surgical transfer to the uteri of pseudopregnant surrogate mothers, the latter developed to term and adult mice. In both cases, animals were obtained that had developed an M-MuLV induced leukemia.

Molecular hybridization tests for the presence of M-MuLV-specific sequences were conducted on DNA extracted from different tissues of leukemic animals to determine which tissues were successfully infected by the virus. Mice which were infected as newborns carried M-MuLV-specific DNA sequences in “target tissues” only, i. e., thymus, spleen, lymph nodes or in organs infiltrated by tumor cells, whereas “non-target tissues” did not carry virus-specific sequences. In contrast, when leukemic animals derived from M-MuLV-infected preimplantation embryos were analyzed, virus-specific sequences were detected in target tissues as well as in non-target tissues, such as liver, kidney, brain, testes and the germ line.

To study the expression of the viral DNA integrated in target and non-target organs, RNA was extracted from different tissues of an animal infected at the preimplantation stage. Fifty to 100 times more M-MuLV-specific RNA was de?tected in tumor tissues than was found in non-target organs. Since all organs contained the same amount of virus-specific DNA, these results indicate that the integrated virus genome can be differentially expressed in different tissues. The organ-tropism of RNA tumor viruses is discussed in view of these findings.

Mice that were infected at the preimplantation stage were found to have M-MuLV integrated into their germ line. Virus transmission from the father to the offspring occurred according to simple Mendelian expectations. Molecular hybrid?ization tests revealed that in the animals studied, the virus was integrated into the germ line at only one out of two or three possible integration sites. During the development of leukemia amplification of this virus copy was observed in the target tissues only, but not in the non-target tissues.

Keywords

Sucrose Lymphoma EDTA Leukemia Bromide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Todaro, G., Benveniste, R., Callahan, R., Lieber, M., and Sherr, C. (1974) Cold Spring Harbor Symp. Quant. Biol. 39: 1159.CrossRefGoogle Scholar
  2. 2.
    Gross, L. (1974) Proc. Nat. Acad. Sci. USA 71: 2013.CrossRefGoogle Scholar
  3. 3.
    Rowe, W. (1972) J. Exp. Med. 136: 1272.PubMedCrossRefGoogle Scholar
  4. 4.
    Chattopadhyay, S., Lowy, D., Teich, N., Levine, A., and Rowe, W. (1974) Cold Spring Harbor Symp. Quant. Biol. 39: 1085.CrossRefGoogle Scholar
  5. 5.
    Rubin, H., Fanshier, L., Cornelius, A., and Hughes, W. (1962) Virology 17: 143.PubMedCrossRefGoogle Scholar
  6. 6.
    Buffet, R., Grace, J., DiBerardino, L., and Mirand, E. (1969) Cancer Res. 29: 588.Google Scholar
  7. 7.
    Law, L., and Moloney, B. (1961) Proc. Soc. Exp. Biol. Med. 108: 715.Google Scholar
  8. 8.
    Baluda, M., and Drohan, W. (1972) J. Virol. 10: 1002.PubMedGoogle Scholar
  9. 9.
    Jaenisch, R., Fan, H., and Croker, B. (1975) Proc. Nat. Acad. Sci. USA 72, 4008.Google Scholar
  10. 10.
    Jaenisch, R., and Mintz, B. (1974) Proc. Nat. Acad. Sci. USA 71: 1250.CrossRefGoogle Scholar
  11. 11.
    Jaenisch, R. (1974) Cold Spring Harbor Symp. Quant. Biol. 39: 375.CrossRefGoogle Scholar
  12. 12.
    Fan, H., and Baltimore, D. (1973) J. Mol. Biol. 80: 93.PubMedCrossRefGoogle Scholar
  13. 13.
    Fan, H., and Paskind, M. (1974) J. Virol. 14: 421.PubMedGoogle Scholar
  14. 14.
    Croker, B., DelVillano, B., Jensen, F., and Dixon, F. (1974) J. Exp. Med. 140: 1028.PubMedCrossRefGoogle Scholar
  15. 15.
    Mintz, B. (1971) in Methods in Mammalian Embryology (Daniel, J., ed) (Freeman, San Francisco ), pp. 189–214.Google Scholar
  16. 16.
    Kirby, K. (1966) in Methods in Enzymology 22: 87.Google Scholar
  17. 17.
    Wetmur, J., and Davidson, N. (1968) J. Mol. Biol. 31: 349.PubMedCrossRefGoogle Scholar
  18. 18.
    Tooze, J. (1973) in The Molecular Biology of Tumor Viruses (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York ) p 617.Google Scholar
  19. 19.
    Herbert, M., and Graham, C. (1974) in Current Topics in Develop. Biol. 8: 151Google Scholar
  20. 20.
    Weiss, R. (1975) Perspect. Virol. 9: 165.Google Scholar
  21. 21.
    Benveniste, R., and Todaro, G. (1974) Nature 252: 170.PubMedCrossRefGoogle Scholar
  22. 22.
    Varmus, H., Guntaka, R., Fan, W., Heasley, S., and Bishop, M. (1974) Proc. Nat. Acad. Sci. USA 71: 3874.CrossRefGoogle Scholar
  23. 23.
    Gianni, A., Smotking, D., and Weinberg, R. (1975) Proc. Nat. Acad. Sci. USA 72: 447.CrossRefGoogle Scholar
  24. 24.
    Mintz, B. (1968) J. Animals Science 27, Supplement 1, 51.Google Scholar
  25. 25.
    Britten, R., Dale, G., and Neufeld, R. (1974) in Methods in Enzymology 29: 363.Google Scholar

Copyright information

© J. F. Lehmanns Verlag München 1976

Authors and Affiliations

  • Rudolf Jaenisch
    • 1
    • 2
  • Jessica Dausman
    • 1
    • 2
  • Virginia Cox
    • 1
    • 2
  • Hung Fan
    • 1
    • 2
  1. 1.The Salk InstituteSan DiegoUSA
  2. 2.Byron Croker Scripps Clinic & Research FoundationLa JollaUSA

Personalised recommendations