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. 1981 Jul;39(1):1–10. doi: 10.1128/jvi.39.1.1-10.1981

Characterization of AKR murine leukemia virus sequences in AKR mouse substrains and structure of integrated recombinant genomes in tumor tissues.

W Quint, W Quax, H van der Putten, A Berns
PMCID: PMC171259  PMID: 6268802

Abstract

A specific cDNA probe of AKR murine leukemia virus (AKR-MLV) was prepared to detect AKR-MLV sequences in normal and tumor tissues in a variety of AKR mouse substrains. AKR strains contained up to six endogenous AKR-MLV genomes. All substrains tested had one AKR-MLV locus in common, and closely related substrains had several proviruses integrated in an identical site. Virus-induced tumors in the AKR/FuRdA and AKR/JS strains showed a reintegration pattern of AKR-MLV sequences unique for the individual animal, suggesting a monoclonal origin for the outgrown tumors. An analysis of tumor DNAs from the AKR/FuRdA and AKR/JS substrains with restriction enzymes cleaving within the proviral genome revealed a new EcoRI restriction site and BamHI restriction site not present in normal tissues. The positions of these sites corresponded both with cleavage sites of EcoRI and BamHI in integrated Moloney recombinants and with the structure of isolated AKR mink cell focus-forming viruses. All tumors analyzed to data contain nearly identical integrated recombinant genomes, suggesting a causal relationship between the formation of recombinants and the leukemogenic process.

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Selected References

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  1. Aaronson S. A., Stephenson J. R. Endogenous type-C RNA viruses of mammalian cells. Biochim Biophys Acta. 1976 Dec 23;458(4):323–354. doi: 10.1016/0304-419x(76)90006-8. [DOI] [PubMed] [Google Scholar]
  2. Berns A., Jaenisch R. Increase of AKR-specific sequences in tumor tissues of leukemic AKR mice. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2448–2452. doi: 10.1073/pnas.73.7.2448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bosselman R. A., Van Griensven L. J., Vogt M., Verma I. M. Genome organization of retroviruses. VI. Heteroduplex analysis of ecotropic and xenotropic sequences of moloney mink cell focus-inducing viral RNA obtained from either a cloned isolate or a thymoma cell line. J Virol. 1979 Dec;32(3):968–978. doi: 10.1128/jvi.32.3.968-978.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Canaani E., Aaronson S. A. Restriction enzyme analysis of mouse cellular type C viral DNA: emergence of new viral sequences in spontaneous AKR/J lymphomas. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1677–1681. doi: 10.1073/pnas.76.4.1677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chan H. W., Bryan T., Moore J. L., Staal S. P., Rowe W. P., Martin M. A. Identification of ecotropic proviral sequences in inbred mouse strains with a cloned subgenomic DNA fragment. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5779–5783. doi: 10.1073/pnas.77.10.5779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chattopadhyay S. K., Lander M. R., Rands E., Lowy D. R. Structure of endogenous murine leukemia virus DNA in mouse genomes. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5774–5778. doi: 10.1073/pnas.77.10.5774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chattopadhyay S. K., Lowy D. R., Teich N. M., Levine A. S., Rowe W. P. Qualitative and quantitative studies of AKR-type murine leukemia virus sequences in mouse DNA. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):1085–1101. doi: 10.1101/sqb.1974.039.01.124. [DOI] [PubMed] [Google Scholar]
  8. Chattopadhyay S. K., Rowe W. P., Teich N. M., Lowy D. R. Definitive evidence that the murine C-type virus inducing locus Akv-1 is viral genetic material. Proc Natl Acad Sci U S A. 1975 Mar;72(3):906–910. doi: 10.1073/pnas.72.3.906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cohen J. C., Shank P. R., Morris V. L., Cardiff R., Varmus H. E. Integration of the DNA of mouse mammary tumor virus in virus-infected normal and neoplastic tissue of the mouse. Cell. 1979 Feb;16(2):333–345. doi: 10.1016/0092-8674(79)90010-2. [DOI] [PubMed] [Google Scholar]
  10. Donoghue D. J., Rothenberg E., Hopkins N., Baltimore D., Sharp P. A. Heteroduplex analysis of the nonhomology region between Moloney MuLV and the dual host range derivative HIX virus. Cell. 1978 Aug;14(4):959–970. doi: 10.1016/0092-8674(78)90350-1. [DOI] [PubMed] [Google Scholar]
  11. Fan H., Verma I. M. Size analysis and relationship of murine leukemia virus-specific mRNA's: evidence for transposition of sequences during synthesis and processing of subgenomic mRNA. J Virol. 1978 May;26(2):468–478. doi: 10.1128/jvi.26.2.468-478.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hartley J. W., Wolford N. K., Old L. J., Rowe W. P. A new class of murine leukemia virus associated with development of spontaneous lymphomas. Proc Natl Acad Sci U S A. 1977 Feb;74(2):789–792. doi: 10.1073/pnas.74.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Haseltine W. A., Pedersen F. S., Sahagan B. G., Rosenberg Z. F., Kozlov J. Comparative analysis of RNA tumor virus genomes. Haematol Blood Transfus. 1979;23:529–552. doi: 10.1007/978-3-642-67057-2_70. [DOI] [PubMed] [Google Scholar]
  14. Ihle J. N., Joseph D. R. Serological and virological analysis of NIH (NIH X AKR) mice: evidence for three AKR murine leukemia virus loci. Virology. 1978 Jun 15;87(2):287–297. doi: 10.1016/0042-6822(78)90134-4. [DOI] [PubMed] [Google Scholar]
  15. Jähner D., Stuhlmann H., Jaenisch R. Conformation of free and of integrated Moloney leukemia virus proviral DNA in preleukemic and leukemic BALB/Mo mice. Virology. 1980 Feb;101(1):111–123. doi: 10.1016/0042-6822(80)90488-2. [DOI] [PubMed] [Google Scholar]
  16. Lowy D. R., Chattopadhyay S. K., Teich N. M., Rowe W. P., Levine A. S. AKR murine leukemia virus genome: frequency of sequences in DNA of high-, low-, and non-virus-yielding mouse strains. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3555–3559. doi: 10.1073/pnas.71.9.3555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lowy D. R., Rands E., Chattopadhyay S. K., Garon C. F., Hager G. L. Molecular cloning of infectious integrated murine leukemia virus DNA from infected mouse cells. Proc Natl Acad Sci U S A. 1980 Jan;77(1):614–618. doi: 10.1073/pnas.77.1.614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lung M. L., Hering C., Hartley J. W., Rowe W. P., Hopkins N. Analysis of the genomes of mink cell focus-inducing murine type-C viruses: a progress report. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):1269–1274. doi: 10.1101/sqb.1980.044.01.138. [DOI] [PubMed] [Google Scholar]
  19. Morris V. L., Vlasschaert J. E., Beard C. L., Milazzo M. F., Bradbury W. C. Mammary tumors from BALB/c mice with a reported high mammary tumor incidence have acquired new mammary tumor virus DNA sequences. Virology. 1980 Jan 15;100(1):101–109. doi: 10.1016/0042-6822(80)90555-3. [DOI] [PubMed] [Google Scholar]
  20. Pedersen F. S., Buchhagen D. L., Chen C. Y., Hays E. F., Haseltine W. A. Characterization of virus produced by a lymphoma induced by inoculation of AKR MCF-247 virus. J Virol. 1980 Jul;35(1):211–218. doi: 10.1128/jvi.35.1.211-218.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Robbins K. C., Cabradilla C. D., Stephenson J. R., Aaronson S. A. Segregation of genetic information for a B-tropic leukemia virus with the structural locus for BALB:virus-1. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2953–2957. doi: 10.1073/pnas.74.7.2953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rommelaere J., Faller D. V., Hopkins N. Characterization and mapping of RNase T1-resistant oligonucleotides derived from the genomes of Akv and MCF murine leukemia viruses. Proc Natl Acad Sci U S A. 1978 Jan;75(1):495–499. doi: 10.1073/pnas.75.1.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rowe W. P., Kozak C. A. Germ-line reinsertions of AKR murine leukemia virus genomes in Akv-1 congenic mice. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4871–4874. doi: 10.1073/pnas.77.8.4871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rowe W. P., Pincus T. Quantitative studies of naturally occurring murine leukemia virus infection of AKR mice. J Exp Med. 1972 Feb 1;135(2):429–436. doi: 10.1084/jem.135.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  26. Steffen D. L., Bird S., Weinberg R. A. Evidence for the Asiatic origin of endogenous AKR-type murine leukemia proviruses. J Virol. 1980 Sep;35(3):824–835. doi: 10.1128/jvi.35.3.824-835.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Steffen D., Bird S., Rowe W. P., Weinberg R. A. Identification of DNA fragments carrying ecotropic proviruses of AKR mice. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4554–4558. doi: 10.1073/pnas.76.9.4554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sutcliffe J. G., Shinnick T. M., Verma I. M., Lerner R. A. Nucleotide sequence of Moloney leukemia virus: 3' end reveals details of replications, analogy to bacterial transposons, and an unexpected gene. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3302–3306. doi: 10.1073/pnas.77.6.3302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Swanstrom R., Shank P. R. X-Ray Intensifying Screens Greatly Enhance the Detection by Autoradiography of the Radioactive Isotopes 32P and 125I. Anal Biochem. 1978 May;86(1):184–192. doi: 10.1016/0003-2697(78)90333-0. [DOI] [PubMed] [Google Scholar]
  30. Van Beveren C., Goddard J. G., Berns A., Verma I. M. Structure of Moloney murine leukemia viral DNA: nucleotide sequence of the 5' long terminal repeat and adjacent cellular sequences. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3307–3311. doi: 10.1073/pnas.77.6.3307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. van der Putten H., Terwindt E., Berns A., Jaenisch R. The integration sites of endogenous and exogenous Moloney murine leukemia virus. Cell. 1979 Sep;18(1):109–116. doi: 10.1016/0092-8674(79)90359-3. [DOI] [PubMed] [Google Scholar]

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