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. 1986 May;58(2):247–252. doi: 10.1128/jvi.58.2.247-252.1986

Transfer, by selective breeding, of the pathogenic Mtv-2 endogenous provirus from the GR strain to a wild mouse line free of endogenous and exogenous mouse mammary tumor virus.

D W Morris, L J Young, M B Gardner, R D Cardiff
PMCID: PMC252907  PMID: 3009842

Abstract

The GR laboratory mouse strain has five endogenous proviral copies of the mouse mammary tumor virus (MMTV). One of these, Mtv-2, is unique because it causes mammary carcinomas in virtually 100% of breeding GR females prior to 1 year of age. To facilitate studies of this locus in particular, and mammary tumorigenesis in general, we genetically tailored a new mouse line, WXG-2, which bears Mtv-2 as its only endogenous MMTV provirus. The WXG-2 line was constructed by making hybrids between the GR strain and a wild mouse line free of both endogenous and exogenous MMTV, backcrossing to the MMTV-free line, and fixing the Mtv-2 locus in a population with the desired genotype. Mammary tumors were observed in 5 of the 20 hybrid females carrying the endogenous Mtv-2 provirus. The WXG-2 line represents a new model system for studying MMTV-induced mammary tumorigenesis in the absence of multiple endogenous proviruses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ANDERVONT H. B. Biological studies on the mammary tumor inciter in mice. Ann N Y Acad Sci. 1952 Jul 10;54(6):1004–1011. doi: 10.1111/j.1749-6632.1952.tb39975.x. [DOI] [PubMed] [Google Scholar]
  2. Callahan R., Gallahan D., Kozak C. Two genetically transmitted BALB/c mouse mammary tumor virus genomes located on chromosomes 12 and 16. J Virol. 1984 Mar;49(3):1005–1008. doi: 10.1128/jvi.49.3.1005-1008.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cardiff R. D., Fanning T. G., Morris D. W., Ashley R. L., Faulkin L. J. Restriction endonuclease studies of hyperplastic outgrowth lines from BALB/cfC3H mouse hyperplastic mammary nodules. Cancer Res. 1981 Aug;41(8):3024–3029. [PubMed] [Google Scholar]
  4. Cardiff R. D., Morris D. W., Young L. J. Alterations of acquired mouse mammary tumor virus DNA during mammary tumorigenesis in BALB/cfC3H mice. J Natl Cancer Inst. 1983 Nov;71(5):1011–1019. [PubMed] [Google Scholar]
  5. 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]
  6. Cohen J. C., Traina V. L., Breznik T., Gardner M. Development of a mouse mammary tumor virus-negative mouse strain: a new system for the study of mammary carcinogenesis. J Virol. 1982 Dec;44(3):882–885. doi: 10.1128/jvi.44.3.882-885.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cohen J. C., Varmus H. E. Endogenous mammary tumour virus DNA varies among wild mice and segregates during inbreeding. Nature. 1979 Mar 29;278(5703):418–423. doi: 10.1038/278418a0. [DOI] [PubMed] [Google Scholar]
  8. Cohen J. C., Varmus H. E. Proviruses of mouse mammary tumor virus in normal and neoplastic tissues from GR and C3Hf mouse strains. J Virol. 1980 Aug;35(2):298–305. doi: 10.1128/jvi.35.2.298-305.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Etkind P. R., Sarkar N. H. Integration of new endogenous mouse mammary tumor virus proviral DNA at common sites in the DNA of mammary tumors of C3Hf mice and hypomethylation of the endogenous mouse mammary tumor virus proviral DNA in C3Hf mammary tumors and spleens. J Virol. 1983 Jan;45(1):114–123. doi: 10.1128/jvi.45.1.114-123.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fanning T. G., Puma J. P., Cardiff R. D. Identification and partial characterization of an endogenous form of mouse mammary tumor virus that is transcribed into the virion-associated RNA genome. Nucleic Acids Res. 1980 Dec 11;8(23):5715–5723. doi: 10.1093/nar/8.23.5715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fanning T. G., Puma J. P., Cardiff R. D. Selective amplification of mouse mammary tumor virus in mammary tumors of GR mice. J Virol. 1980 Oct;36(1):109–114. doi: 10.1128/jvi.36.1.109-114.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fanning T. G., Vassos A. B., Cardiff R. D. Methylation and amplification of mouse mammary tumor virus DNA in normal, premalignant, and malignant cells of GR/A mice. J Virol. 1982 Mar;41(3):1007–1013. doi: 10.1128/jvi.41.3.1007-1013.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Faulkin L. J., Mitchell D. J., Young L. J., Morris D. W., Malone R. W., Cardiff R. D., Gardner M. B. Hyperplastic and neoplastic changes in the mammary glands of feral mice free of endogenous mouse mammary tumor virus provirus. J Natl Cancer Inst. 1984 Oct;73(4):971–982. [PubMed] [Google Scholar]
  14. Gardner M. B., Malone R. W., Morris D. W., Young L. J., Strange R., Cardiff R. D., Faulkin L. J., Mitchell D. J. Mammary tumors in feral mice lacking MuMTV DNA. J Exp Pathol. 1985 Summer;2(2):93–98. [PubMed] [Google Scholar]
  15. Gardner M. B., Rasheed S. Retroviruses in feral mice. Int Rev Exp Pathol. 1982;23:209–267. [PubMed] [Google Scholar]
  16. Groner B., Hynes N. E. Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors. J Virol. 1980 Mar;33(3):1013–1025. doi: 10.1128/jvi.33.3.1013-1025.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Heston W. E., Parks W. P. Mammary tumors and mammary tumor virus expression in hybrid mice of strains C57BL and GR. J Exp Med. 1977 Nov 1;146(5):1206–1220. doi: 10.1084/jem.146.5.1206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Heston W. E., Smith B., Parks W. P. Mouse mammary tumor virus in hybrids from strains C57BL and GR: breeding test of backcross segregants. J Exp Med. 1976 Oct 1;144(4):1022–1030. doi: 10.1084/jem.144.4.1022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hilgers J., Bentvelzen P. Interaction between viral and genetic factors in murine mammary cancer. Adv Cancer Res. 1978;26:143–195. doi: 10.1016/s0065-230x(08)60087-1. [DOI] [PubMed] [Google Scholar]
  20. Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. MacInnes J. I., Morris V. L., Flintoff W. F., Kozak C. A. Characterization and chromosomal location of endogenous mouse mammary tumor virus loci in GR, NFS, and DBA mice. Virology. 1984 Jan 15;132(1):12–25. doi: 10.1016/0042-6822(84)90087-4. [DOI] [PubMed] [Google Scholar]
  22. Macinnes J. I., Chan E. C., Percy D. H., Morris V. L. Mammary tumors from GR mice contain more than one population of mouse mammary tumor virus-infected cells. Virology. 1981 Aug;113(1):119–129. doi: 10.1016/0042-6822(81)90141-0. [DOI] [PubMed] [Google Scholar]
  23. Majors J. E., Varmus H. E. Nucleotide sequences at host-proviral junctions for mouse mammary tumour virus. Nature. 1981 Jan 22;289(5795):253–258. doi: 10.1038/289253a0. [DOI] [PubMed] [Google Scholar]
  24. Michalides R., Verstraeten R., Shen F. W., Hilgers J. Characterization and chromosomal distribution of endogenous mouse mammary tumor viruses of European mouse strains STS/A and GR/A. Virology. 1985 Apr 30;142(2):278–290. doi: 10.1016/0042-6822(85)90336-8. [DOI] [PubMed] [Google Scholar]
  25. Michalides R., Wagenaar E., Sluyser M. Mammary tumor virus DNA as a marker for genotypic variance within hormone-responsive GR mouse mammary tumors. Cancer Res. 1982 Mar;42(3):1154–1158. [PubMed] [Google Scholar]
  26. Michalides R., van Nie R., Nusse R., Hynes N. E., Groner B. Mammary tumor induction loci in GR and DBAf mice contain one provirus of the mouse mammary tumor virus. Cell. 1981 Jan;23(1):165–173. doi: 10.1016/0092-8674(81)90281-6. [DOI] [PubMed] [Google Scholar]
  27. Mühlbock O. Note on a new inbred mouse-strain GR-A. Eur J Cancer. 1965 Oct;1(2):123–124. doi: 10.1016/0014-2964(65)90003-4. [DOI] [PubMed] [Google Scholar]
  28. Nandi S., Helmich C. Transmission of the mammary tumor virus by the GR mouse strain. II. Genetic studies. J Natl Cancer Inst. 1974 May;52(5):1567–1570. doi: 10.1093/jnci/52.5.1567. [DOI] [PubMed] [Google Scholar]
  29. Nusse R., Varmus H. E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982 Nov;31(1):99–109. doi: 10.1016/0092-8674(82)90409-3. [DOI] [PubMed] [Google Scholar]
  30. Nusse R., de Moes J., Hilkens J., van Nie R. Localization of a gene for expression of mouse mammary tumor virus antigens in the GR/Mtv-2- mouse strain. J Exp Med. 1980 Sep 1;152(3):712–719. doi: 10.1084/jem.152.3.712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Peters G., Brookes S., Smith R., Dickson C. Tumorigenesis by mouse mammary tumor virus: evidence for a common region for provirus integration in mammary tumors. Cell. 1983 Jun;33(2):369–377. doi: 10.1016/0092-8674(83)90418-x. [DOI] [PubMed] [Google Scholar]
  32. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  33. Ringold G. M. Regulation of mouse mammary tumor virus gene expression by glucocorticoid hormones. Curr Top Microbiol Immunol. 1983;106:79–103. doi: 10.1007/978-3-642-69357-1_4. [DOI] [PubMed] [Google Scholar]
  34. Sass B., Dunn T. B. Classification of mouse mammary tumors in Dunn's miscellaneous group including recently reported types. J Natl Cancer Inst. 1979 May;62(5):1287–1293. [PubMed] [Google Scholar]
  35. 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]
  36. St George J. A., Cardiff R. D., Young L. J., Faulkin L. J. Immunocytochemical distribution of mouse mammary tumor virus antigens in BALB/cfC3H mammary epithelium. J Natl Cancer Inst. 1979 Sep;63(3):813–820. doi: 10.1093/jnci/63.3.813. [DOI] [PubMed] [Google Scholar]
  37. Staats J. Standardized nomenclature for inbred strains of mice: seventh listing for the International Committee on Standardized Genetic Nomenclature for Mice. Cancer Res. 1980 Jul;40(7):2083–2128. [PubMed] [Google Scholar]
  38. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Traina-Dorge V., Cohen J. C. Molecular genetics of mouse mammary tumor virus. Curr Top Microbiol Immunol. 1983;106:35–56. doi: 10.1007/978-3-642-69357-1_2. [DOI] [PubMed] [Google Scholar]
  40. Van Nie R., Verstraeten A. A., De Moes J. Genetic transmission of mammary tumour virus by GR mice. Int J Cancer. 1977 Mar 15;19(3):383–390. doi: 10.1002/ijc.2910190316. [DOI] [PubMed] [Google Scholar]
  41. van Nie R., de Moes J. Development of a congeneic line of the GR mouse strain without early mammary tumours. Int J Cancer. 1977 Oct 15;20(4):588–594. doi: 10.1002/ijc.2910200417. [DOI] [PubMed] [Google Scholar]

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