Abstract
We present a general strategy for the efficient insertion of recombinant retroviral vector DNA into the mouse germ line via infection of preimplantation mouse embryos. Transgenic mice were generated that harbor a replication-competent recombinant retrovirus (delta Mo + Py M-MuLV) that lacks the Moloney murine leukemia virus (M-MuLV)-type enhancer sequence in the long terminal repeat (LTR). Instead, the LTR contains an enhancer element that permits polyoma virus F101 to grow in undifferentiated F9 embryonal carcinoma cells. Expression studies in different tissues of animals transgenic for delta Mo + Py M-MuLV indicate possibilities to target and modulate expression of retroviral recombinants in mice via their LTR enhancer sequences. In addition, 16 transgenic mice were generated that harbor proviral DNA of a defective recombinant retrovirus carrying a mutant dihydrofolate reductase gene.
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- Bishayee S., Strand M., August J. T. Cellular membrane receptors for oncovirus envelope glycoprotein: properties of the binding reaction and influence of different reagents on the substrate and the receptors. Arch Biochem Biophys. 1978 Jul;189(1):161–171. doi: 10.1016/0003-9861(78)90129-7. [DOI] [PubMed] [Google Scholar]
- Cepko C. L., Roberts B. E., Mulligan R. C. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell. 1984 Jul;37(3):1053–1062. doi: 10.1016/0092-8674(84)90440-9. [DOI] [PubMed] [Google Scholar]
- Chatis P. A., Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408–4411. doi: 10.1073/pnas.80.14.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chatis P. A., Holland C. A., Silver J. E., Frederickson T. N., Hopkins N., Hartley J. W. A 3' end fragment encompassing the transcriptional enhancers of nondefective Friend virus confers erythroleukemogenicity on Moloney leukemia virus. J Virol. 1984 Oct;52(1):248–254. doi: 10.1128/jvi.52.1.248-254.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cone R. D., Mulligan R. C. High-efficiency gene transfer into mammalian cells: generation of helper-free recombinant retrovirus with broad mammalian host range. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6349–6353. doi: 10.1073/pnas.81.20.6349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cuypers H. T., Selten G., Quint W., Zijlstra M., Maandag E. R., Boelens W., van Wezenbeek P., Melief C., Berns A. Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region. Cell. 1984 May;37(1):141–150. doi: 10.1016/0092-8674(84)90309-x. [DOI] [PubMed] [Google Scholar]
- Davis B., Linney E., Fan H. Suppression of leukaemia virus pathogenicity by polyoma virus enhancers. Nature. 1985 Apr 11;314(6011):550–553. doi: 10.1038/314550a0. [DOI] [PubMed] [Google Scholar]
- DesGroseillers L., Jolicoeur P. The tandem direct repeats within the long terminal repeat of murine leukemia viruses are the primary determinant of their leukemogenic potential. J Virol. 1984 Dec;52(3):945–952. doi: 10.1128/jvi.52.3.945-952.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DesGroseillers L., Rassart E., Jolicoeur P. Thymotropism of murine leukemia virus is conferred by its long terminal repeat. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4203–4207. doi: 10.1073/pnas.80.14.4203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujimura F. K., Deininger P. L., Friedmann T., Linney E. Mutation near the polyoma DNA replication origin permits productive infection of F9 embryonal carcinoma cells. Cell. 1981 Mar;23(3):809–814. doi: 10.1016/0092-8674(81)90445-1. [DOI] [PubMed] [Google Scholar]
- Gautsch J. W., Wilson M. C. Delayed de novo methylation in teratocarcinoma suggests additional tissue-specific mechanisms for controlling gene expression. Nature. 1983 Jan 6;301(5895):32–37. doi: 10.1038/301032a0. [DOI] [PubMed] [Google Scholar]
- Hellerman J. G., Cone R. C., Potts J. T., Jr, Rich A., Mulligan R. C., Kronenberg H. M. Secretion of human parathyroid hormone from rat pituitary cells infected with a recombinant retrovirus encoding preproparathyroid hormone. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5340–5344. doi: 10.1073/pnas.81.17.5340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoppe P. C., Pitts S. Fertilization in vitro and development of mouse ova. Biol Reprod. 1973 May;8(4):420–426. doi: 10.1093/biolreprod/8.4.420. [DOI] [PubMed] [Google Scholar]
- Jaenisch R., Fan H., Croker B. Infection of preimplantation mouse embryos and of newborn mice with leukemia virus: tissue distribution of viral DNA and RNA and leukemogenesis in the adult animal. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4008–4012. doi: 10.1073/pnas.72.10.4008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaenisch R. Germ line integration and Mendelian transmission of the exogenous Moloney leukemia virus. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1260–1264. doi: 10.1073/pnas.73.4.1260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaenisch R., Jähner D. Methylation, expression and chromosomal position of genes in mammals. Biochim Biophys Acta. 1984 May 15;782(1):1–9. doi: 10.1016/0167-4781(84)90099-x. [DOI] [PubMed] [Google Scholar]
- Jaenisch R., Jähner D., Nobis P., Simon I., Löhler J., Harbers K., Grotkopp D. Chromosomal position and activation of retroviral genomes inserted into the germ line of mice. Cell. 1981 May;24(2):519–529. doi: 10.1016/0092-8674(81)90343-3. [DOI] [PubMed] [Google Scholar]
- Jaenisch R. Retroviruses and embryogenesis: microinjection of Moloney leukemia virus into midgestation mouse embryos. Cell. 1980 Jan;19(1):181–188. doi: 10.1016/0092-8674(80)90399-2. [DOI] [PubMed] [Google Scholar]
- Jähner D., Stuhlmann H., Stewart C. L., Harbers K., Löhler J., Simon I., Jaenisch R. De novo methylation and expression of retroviral genomes during mouse embryogenesis. Nature. 1982 Aug 12;298(5875):623–628. doi: 10.1038/298623a0. [DOI] [PubMed] [Google Scholar]
- Lenz J., Celander D., Crowther R. L., Patarca R., Perkins D. W., Haseltine W. A. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. 1984 Mar 29-Apr 4Nature. 308(5958):467–470. doi: 10.1038/308467a0. [DOI] [PubMed] [Google Scholar]
- Lewis S., Gifford A., Baltimore D. Joining of V kappa to J kappa gene segments in a retroviral vector introduced into lymphoid cells. 1984 Mar 29-Apr 4Nature. 308(5958):425–428. doi: 10.1038/308425a0. [DOI] [PubMed] [Google Scholar]
- Linney E., Davis B., Overhauser J., Chao E., Fan H. Non-function of a Moloney murine leukaemia virus regulatory sequence in F9 embryonal carcinoma cells. 1984 Mar 29-Apr 4Nature. 308(5958):470–472. doi: 10.1038/308470a0. [DOI] [PubMed] [Google Scholar]
- Mann R., Mulligan R. C., Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell. 1983 May;33(1):153–159. doi: 10.1016/0092-8674(83)90344-6. [DOI] [PubMed] [Google Scholar]
- Miller A. D., Eckner R. J., Jolly D. J., Friedmann T., Verma I. M. Expression of a retrovirus encoding human HPRT in mice. Science. 1984 Aug 10;225(4662):630–632. doi: 10.1126/science.6377498. [DOI] [PubMed] [Google Scholar]
- Miller A. D., Jolly D. J., Friedmann T., Verma I. M. A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT): gene transfer into cells obtained from humans deficient in HPRT. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4709–4713. doi: 10.1073/pnas.80.15.4709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller A. D., Law M. F., Verma I. M. Generation of helper-free amphotropic retroviruses that transduce a dominant-acting, methotrexate-resistant dihydrofolate reductase gene. Mol Cell Biol. 1985 Mar;5(3):431–437. doi: 10.1128/mcb.5.3.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller A. D., Ong E. S., Rosenfeld M. G., Verma I. M., Evans R. M. Infectious and selectable retrovirus containing an inducible rat growth hormone minigene. Science. 1984 Sep 7;225(4666):993–998. doi: 10.1126/science.6089340. [DOI] [PubMed] [Google Scholar]
- Nicolson G. L., Yanagimachi R., Yanagimachi H. Ultrastructural localization of lectin-binding sites on the zonae pellucidae and plasma membranes of mammalian eggs. J Cell Biol. 1975 Aug;66(2):263–274. doi: 10.1083/jcb.66.2.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Niwa O., Yokota Y., Ishida H., Sugahara T. Independent mechanisms involved in suppression of the Moloney leukemia virus genome during differentiation of murine teratocarcinoma cells. Cell. 1983 Apr;32(4):1105–1113. doi: 10.1016/0092-8674(83)90294-5. [DOI] [PubMed] [Google Scholar]
- Ornitz D. M., Palmiter R. D., Hammer R. E., Brinster R. L., Swift G. H., MacDonald R. J. Specific expression of an elastase-human growth hormone fusion gene in pancreatic acinar cells of transgenic mice. Nature. 1985 Feb 14;313(6003):600–602. doi: 10.1038/313600a0. [DOI] [PubMed] [Google Scholar]
- Scholnick S. B., Morgan B. A., Hirsh J. The cloned dopa decarboxylase gene is developmentally regulated when reintegrated into the Drosophila genome. Cell. 1983 Aug;34(1):37–45. doi: 10.1016/0092-8674(83)90134-4. [DOI] [PubMed] [Google Scholar]
- Simonsen C. C., Levinson A. D. Isolation and expression of an altered mouse dihydrofolate reductase cDNA. Proc Natl Acad Sci U S A. 1983 May;80(9):2495–2499. doi: 10.1073/pnas.80.9.2495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sorge J., Cutting A. E., Erdman V. D., Gautsch J. W. Integration-specific retrovirus expression in embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6627–6631. doi: 10.1073/pnas.81.21.6627. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sorge J., Wright D., Erdman V. D., Cutting A. E. Amphotropic retrovirus vector system for human cell gene transfer. Mol Cell Biol. 1984 Sep;4(9):1730–1737. doi: 10.1128/mcb.4.9.1730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stuhlmann H., Cone R., Mulligan R. C., Jaenisch R. Introduction of a selectable gene into different animal tissue by a retrovirus recombinant vector. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7151–7155. doi: 10.1073/pnas.81.22.7151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Toyoshima K., Vogt P. K. Enhancement and inhibition of avian sarcoma viruses by polycations and polyanions. Virology. 1969 Jul;38(3):414–426. doi: 10.1016/0042-6822(69)90154-8. [DOI] [PubMed] [Google Scholar]
- Ullrich A., Shine J., Chirgwin J., Pictet R., Tischer E., Rutter W. J., Goodman H. M. Rat insulin genes: construction of plasmids containing the coding sequences. Science. 1977 Jun 17;196(4296):1313–1319. doi: 10.1126/science.325648. [DOI] [PubMed] [Google Scholar]
- Wagner E. F., Covarrubias L., Stewart T. A., Mintz B. Prenatal lethalities in mice homozygous for human growth hormone gene sequences integrated in the germ line. Cell. 1983 Dec;35(3 Pt 2):647–655. doi: 10.1016/0092-8674(83)90097-1. [DOI] [PubMed] [Google Scholar]
- Williams D. A., Lemischka I. R., Nathan D. G., Mulligan R. C. Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse. Nature. 1984 Aug 9;310(5977):476–480. doi: 10.1038/310476a0. [DOI] [PubMed] [Google Scholar]
- van der Putten H., Botteri F., Illmensee K. Developmental fate of a human insulin gene in a transgenic mouse. Mol Gen Genet. 1984;198(2):128–138. doi: 10.1007/BF00328712. [DOI] [PubMed] [Google Scholar]
- van der Putten H., Quint W., van Raaij J., Maandag E. R., Verma I. M., Berns A. M-MuLV-induced leukemogenesis: integration and structure of recombinant proviruses in tumors. Cell. 1981 Jun;24(3):729–739. doi: 10.1016/0092-8674(81)90099-4. [DOI] [PubMed] [Google Scholar]







