Molecular Neurobiology

, Volume 2, Issue 3, pp 155–182 | Cite as

Retroviral-mediated gene transfer

Applications in neurobiology
  • Mathew M. S. Lo
  • Mary K. Conrad
  • Cleanthi Mamalaki
  • Michael J. Kadan


There are now many examples of the successful expression of genes transduced by retroviruses in studies from outside the field of neuroscience. Retroviruses will undoubtedly also prove to be effective tools for neuroscientists interested in expressing cloned neurotransmitter and receptor genes. There are also other less obvious applications of retroviruses, such as their insertional mutagenic effects, which may be useful in studies of the genetic factors and biochemical mechanisms involved in, for example, neurotoxicity. Strong cellular promoters have been identified by retroviral infection and subsequent rescue of the flanking genomic DNA. Retroviruses can be employed again to reintroduce these regulatory sequences back into cells. In this way the complexities of gene expression in the many subpopulations of neurons may be unraveled. Retroviruses can also serve as very useful genetic markers in studies of development and lineage relationships. Retroviruses may be used to efficiently transfer oncogenes into neuronal cells to create new cell lines. This application exploits one of the natural traits of retroviruses—oncogenesis—which led to their original discovery. Finally, there are neurotropic retroviruses that could serve as important vectors for delivering genes into neurons. Studying these retroviruses may lead to an understanding of how they cause neuropathologic changes in the CNS.

Index Entries

Gene transfer retroviral vectors insertion mutagens lineage analysis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anderson W. F., Killos L., Sanders-Haigh L., Kretschmer P. J., Diacumakos E. G. (1980), Replication and expression of thymidine kinase and human globin genes microinjected into mouse fibroblasts.Proc. Natl. Acad. Sci. USA 77, 5399–5403.PubMedCrossRefGoogle Scholar
  2. Ayala F. J. and Kreiger J. A. (1984), Genetics with Somatic Cells: Mapping the Human Genome,Modern Genetics. Ayala, F. J., ed., Benjamin/ Cummings, Pub. Co., CT, pp. 579–622.Google Scholar
  3. Barklis E., Mulligan R. C., and Jaenisch R. (1986), Chromosomal position or virus mutation permits retrovirus expression in embryonal carcinoma cells.Cell,47, 391–399.PubMedCrossRefGoogle Scholar
  4. Berger, S. A. and Berstein, A. (1985), Characterization of a retrovirus shuttle vector capable of either proviral integration or extrachromosomal replication in mouse cells.Mol. Cell. Biol. 5, 305–312.PubMedGoogle Scholar
  5. Bitler C. M., Zhang M. B., and Howard B. D. (1986), PC12 variants deficient in catecholamine transport.J. Neurochem. 47, 1286–1293.PubMedGoogle Scholar
  6. Breindl M., Nath, D., Jähner D., and Jaenisch R. (1982), DNase I sensitivity of endogenous and exogenous proviral genome copies inM-MuLV-induced tumors of Mov-3 mice.Virology 71, 204–208.CrossRefGoogle Scholar
  7. Breindl M., Harbers, K., and Jaenisch R. (1984), Retrovirus-induced lethal mutation in collagen I gene of mice is associated with an altered chromatin structure.Cell 38, 9–16.PubMedCrossRefGoogle Scholar
  8. Boeke J. D., Garfinkel D. J., Styles C. A., and Fink G. R. (1985),Ty elements transpose through an RNA intermediate.Cell 40, 491–500.PubMedCrossRefGoogle Scholar
  9. Brown P. O., Bowerman B., Varmus H. E., and Bishop J. M. (1987), Correct integration of retroviral RNAin vitro.Cell 49, 347–356.PubMedCrossRefGoogle Scholar
  10. Bukhari A., Shapiro J., and Adhya S. (1977),DNA Insertion Elements, Pasmids and Episomes, Cold Spring Harbor Laboratory, New York.Google Scholar
  11. Canaani E., Dreazen O., Klar A., Rechavi G., Rain D., Cohen J. B., and Givol D. (1985), Activation of the c-mos oncogene in a mouse plasmacytoma by insertion of an edogenous intracisternal A-particle genome.Proc. Natl Acad. Sci. 80, 7118–7122.CrossRefGoogle Scholar
  12. Cepko C. P., Roberts B. E., and Mulligan R. C. (1984), Construction and applications of a highly transmissible murine retrovirus shuttle vector.Cell 37, 1053–1062.PubMedCrossRefGoogle Scholar
  13. Chiba K., Trevor A., and Castagnoli N. (1984), Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase.Biochem. Biophys, Res. Commun. 120, 574–578.CrossRefGoogle Scholar
  14. Cone R. D. and Mulligan R. C. (1984), High-efficiency gene transfer into mammalian cells: Generation of helper-free recombinant retrovirus with broad mammalian host range.Proc. Natl. Acad. Sci. USA 81, 6349–6353.PubMedCrossRefGoogle Scholar
  15. Copeland N. G., Hutchison K. W., and Jenkins N. A. (1983a), Excision of the DBA ecotropic provirus in dilute coat-color revertants of mice occurs by homologous recombination involving the viral LTRs.Cell 33, 379–387.PubMedCrossRefGoogle Scholar
  16. Copeland N. G., Jenkins N. A., and Lee B. K. (1983b), Association of the lethal yellow (Ay) coat color mutation with an ecotropic murine leukemia virus genome.Proc. Natl. Acad. Sci. USA 80, 247–249.PubMedCrossRefGoogle Scholar
  17. Corcoran L. M., Adams J. M., Dunn A. R., and Cory S. (1984), Murine T lymphomas in which the cellularmyc oncogen has been activated by retroviral insertion.Cell 37, 113–122.PubMedCrossRefGoogle Scholar
  18. Davis G. C., Williams A. C., Markey S. P., Ebert M. H., Caine E. D., Reichert C. M., and Kopin I. J. (1979), Chronic parkinsonism secondary to intraveneous injection of meperidine analogues.Psychiatry Res. 1, 249–254.PubMedCrossRefGoogle Scholar
  19. Denton T. and Howard B. (1984), Inhibition of dopamine uptake by MPTP, a cause of parkinsonism.Biochem. Biophys. Res. Com-mun. 119, 1186–1190.CrossRefGoogle Scholar
  20. Denton T. and Howard B. D. (1987), A dopaminergic cell line variant resistant to the neurotoxinmethyl-4-phenyl-1,2,3,6 tetrahydropyridine.J. Neurochem. 49, 622–630.PubMedCrossRefGoogle Scholar
  21. Dick J. E., Magli M. C., Huszar D., Phillips R. A., and Bernstein A. (1985), Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/W mice.Cell 42, 71–79.PubMedCrossRefGoogle Scholar
  22. Dickson C., Smith R., Brookes S., and Peters G. (1984), Tumorigenesis by mouse mammalry tumor virus: Proviral activation of a cellular gene in the common integration regionint-2.Cell 37, 529–536.PubMedCrossRefGoogle Scholar
  23. Doehmer J., Barinaga M., Vale W., Rosenfeld M. G., Verma I. M., and Evans R. (1982), Introduction of rat growth hormone gene into mouse fibroblasts via a retroviral DNA vector: Expression and regulation.Proc. Natl. Acad. Sci. 79, 2268–2272.PubMedCrossRefGoogle Scholar
  24. Elgin S. C. R. (1981), DNase-1-hypersensitive sites of chromatin.Cell 27, 413–415.PubMedCrossRefGoogle Scholar
  25. Flavell A. J. (1984), Role of reverse transcription in the generation of extrachromosomal copiamobile genetic elements.Nature 310, 514–516.PubMedCrossRefGoogle Scholar
  26. Franley R., Subramani S., Berg P. and Papahadjopoulos D. (1980), Introduction of liposome-encapsulated SV40 DNA into cells.J. Biol. Chem. 255, 10431–10435.Google Scholar
  27. Friedman R. L. (1985), Expression of human adenosine deaminase using a transmissible murine retrovirus vector system.Proc. Natl. Acad. Sci. USA 82, 703–707.PubMedCrossRefGoogle Scholar
  28. Fung Y. K. T., Lewis W. G., Kung K. J., and Crittenden L. B. (1983), Activation of the cellular oncogene c-erb B by LTR insertion: Molecular basis for induction of erythroblastosis by avian leukosis virus.Cell 33, 357–368.PubMedCrossRefGoogle Scholar
  29. Gilboa E., Eglitis M. A., Kantoff P. W., and Anderson W. F. (1986), Overview: Transfer and Expression of Cloned Genes Using Retroviral Vectors.Bio-Techniques 4, 504–512.Google Scholar
  30. Glover J. C., Gray G. E., and Sanes J. R. (1987), Patterns of neurogensis in chick optic tectum studied with a retroviral marker.Society for Neuroscience Abstr. 13, 183.Google Scholar
  31. Goff S. P. (1987), Gene isolation by retroviral tagging,Methods in Enzymol, vol 152. Berger, S. L. and Kimmel, A. R., eds., Academic Press, London, pp. 469–481.Google Scholar
  32. Graham F. L. and van der Eb A. J. (1973), A new technique for the assay of infectivity of human adenovirus 5 DNA.Virology 52, 456–467.PubMedCrossRefGoogle Scholar
  33. Greene L. A. and Tischler A. S. (1982), PC12 pheochromocytoma cultures in neurobiological research,Advances in Cellular Neurobiology, vol. 3, Fedoroffs, S. and Hertz, L., eds., Academic Press, pp. 373–414, New York.Google Scholar
  34. Gudnoadottir, M. and Palsson, P. A. (1967), Transmission of maedi by inoculation of a virus grown from maedi-affected lungs.J. Infect. Dis. 117, 1–6.Google Scholar
  35. Harbers K., Kuehn M., Delius H., and Jaenisch R. (1984), Insertion of retrovirus into the first intron of α1 (I) collagen gene leads to embry onic lethal mutation in mice.Proc. Natl. Acad. Sci. USA 81, 1504–1508.PubMedCrossRefGoogle Scholar
  36. Hawley R. G., Shulman M. J., Murialdo H., Gibson D. M. S., and Hozumi N. (1982), Mutant immunoglobulin genes have repetitive DNA elements inserted into their inter vening sequences.Proc. Natl. Acad. Sci. USA 79, 7425–7429.PubMedCrossRefGoogle Scholar
  37. Hayward W. S., Neel B. G., Astrin S. M. (1981), Activation of a cellularonc gene by promoter insertion in ALV-induced lymphoid leukosisNature 290, 475–480.PubMedCrossRefGoogle Scholar
  38. Hellerman J. G., Cone R. C., Potts J. T., Rich A., Mulligan R. C., and Kronenberg H. M. (1984), Secretion of human parathyroid hormone from rat pituitary cells infected with a recombinant retrovirus encoding preproparathyroid hormone.Proc. Natl. Acad. Sci. USA 81, 5340–5344.PubMedCrossRefGoogle Scholar
  39. Hock R. A. and Miller A. D. (1986), Retrovirus mediated transfer and expression of drug resistancegenes in human haemopoetic progenitor cells.Nature 320, 275–277.PubMedCrossRefGoogle Scholar
  40. Hooper M., Hardy K., Handyside A., Hunter S., and Monk M. (1987), HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells.Nature 326, 292–295.PubMedCrossRefGoogle Scholar
  41. Hughes S. H., Shank P. R., Spector D. H., Kung H. J., Bishop J. M., Varmus H. E., Vogt P. K., and Breitman M. L. (1978), Proviruses of avian sarcoma virus are terminally redundant, coextensive with unintegrated linear DNA and integrated at many sites.Cell 15, 1397–1410.PubMedCrossRefGoogle Scholar
  42. Hwang L. H. S. and Gilboa E. (1984), Expression of genes introduced into cells by retroviral infection is more efficient than that of genes introduced into cells by DNA transfection.J. Virol. 50, 417–424.PubMedGoogle Scholar
  43. Ishiura M., Hirose S., Uchida T., Hamada Y., Suzuki Y., and Okada Y. (1982), Phage particlemediated gene transfer to cultured mammalian cells.Mol. Cell. Biol. 2, 607–616.PubMedGoogle Scholar
  44. Jaenisch R., Fan H., and Croker B. (1975), 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. USA 72, 4008–4012.PubMedCrossRefGoogle Scholar
  45. Jaenisch R. (1976), Germ line integration and Mendelian trasmission of the exogenous Moloney leukemia virus.Proc. Natl. Acad. Sci. USA 73, 1260–1264.PubMedCrossRefGoogle Scholar
  46. Jaenisch R. (1980), Retroviruses and Embryogenesis: Microinjection of Moloney leukemia Virus into Midgestation Mouse Embryos.Cell 19, 181–188.PubMedCrossRefGoogle Scholar
  47. Jaenisch R., Harbers K., Schnicke A., Lohler J., Chumakov I., Jahnex D., Grotkopp D., and Hoffmann E. (1983), Germ line integration of Moloney murine leukemia virus at the MOV 13 locus leads to recessive lethal mutation and early embryonic death.Cell 32, 209–216.PubMedCrossRefGoogle Scholar
  48. Jaenisch R., Breindl M., Harbers K., Jahner D., and Lohler J. (1985), Retroviruses and Insertional Mutagenesis.Cold Spring Harbor Sump. 50, 439–445.Google Scholar
  49. Jähner D., Stuhlmann H., Stewart C. L., Harbers K., Löhler T., Simon I., and Jaenisch R. (1982), Denovo methylation and expression of retroviral genomes during mouse embryogenesis.Nature 298, 623–628.PubMedCrossRefGoogle Scholar
  50. Javitch J. A., D’Amato R. J., Strittmatter S. M., and Snyder S. H. (1985), Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity.Proc. Natl. Acad. Sci. USA 82, 2173–2177.PubMedCrossRefGoogle Scholar
  51. Jenkins N. A., Copeland N. G., Taylor B. A., and Lee B. K. (1981), Dilute (d) coat colour mutation of DBA/2Jmice is associated with the site of integration of an ecotropic MuLV genome.Nature 293, 370–374.PubMedCrossRefGoogle Scholar
  52. Kantoff P. W., Kohn D. B., Mitsuya H., Armentano D., Sieberg M., Zwiebel J. A., Eglitis M. A., McLachlin J. R., Wiginton D. A., Hutton J. J., Horowitz S. D., Gilboa E., Blaese R. M., and Anderson W. F. (1986), Correction of adenosine deaminase deficiency in human T and B cells using retroviral-mediated gene transfer.Proc. Natl. Acad. Sci. USA 83, 6563–6567.PubMedCrossRefGoogle Scholar
  53. King W., Patel M. D., Lobel L. I., Goff S. P., and Nguyen-Huu M. C. (1985), Insertion mutagenesis of embryonal carcinoma cells by retroviruses.Science 228, 554–558.PubMedCrossRefGoogle Scholar
  54. Korman A. J., Frantz J. D., Strominger J. L., and Mulligan R. C. (1978), Expression of human class II major histocompatibility complex antigens using retrovirus vectors.Proc. Natl. Acad. Sci. USA 84, 2150–2154.CrossRefGoogle Scholar
  55. Kuehn M. R., Bradley A., Robertson E. J., and Evans M. J. (1987), A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice.Nature 326, 295–298.PubMedCrossRefGoogle Scholar
  56. Kuff E. L., Feenstro A., Luenders K., Smith L., Hawley R., Hozumi N., and Shulman M. (1983), Intracisternal A-particle genes as movable elements in the mouse genome.Proc. Natl. Acad. Sci. 80, 1992–1996.PubMedCrossRefGoogle Scholar
  57. Langston J. W., Ballard P., Tetrud J. W., and Irwin I. (1983), Chronic parkinsonism in humans due to a product of meperidine-analog synthesis.Science 219, 979–980.PubMedCrossRefGoogle Scholar
  58. Ledley F. D., Grenett H. E., McGinnis-Shelnutt M., and Woo S. L. C. (1986), Retroviral-mediated gene transfer of human phenylalanine hydroxylase into NIH 3T3 and hepatoma cells.Proc. Natl. Acad. Sci. 83, 409–413.PubMedCrossRefGoogle Scholar
  59. Linney E., Davis B., Overhauser J., Chao E., and Fan H. (1984), Non-function Moloney murine leukemia virus regulatory sequence in F9 embryonal carcinoma.Nature 308, 470–472.PubMedCrossRefGoogle Scholar
  60. Lo M. M. S., Dersch, C. M., and Mamalaki C. (1987), Retroviral infection in PC12 produces MPTP resistant mutants.Society for Neuroscience Abstr. 13, 78.Google Scholar
  61. Luskin M. B., Pearlman A. L., and Sanes J. R. (1987), Cell lineage in mouse cerebral cortex studied into retroviral marker.Society for Neurscience Abstr. 13, 183.Google Scholar
  62. Majors J. E. and Varmus H. E. (1981), Nucleotide sequences at host-proviral junctions for mouse mammary tumour virus.Nature 289, 253–258.PubMedCrossRefGoogle Scholar
  63. Mamalaki, C., Douglas R. C., Carlson, S. G., Dersch, C. M. and Lo M. M. S. (1987), DNA sequences involved in MPTP neurotoxicity.Society for Neuroscience Abstr. 13, 558.Google Scholar
  64. Mann R., Mulligan R. C., and Baltimore D. (1983), Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus.Cell 33, 153–159.PubMedCrossRefGoogle Scholar
  65. Markey S. P., Johannessen N. J., Chiueh C. C., Burns R. S., and Herkenham M. A. (1984), Intraneuronal generation of a pyridinium metabolite may cause drug induced parkinsonism.Nature 311, 464–467.PubMedCrossRefGoogle Scholar
  66. McCutchen J. H. and Pagano J. S. (1968), Enhancement of the infectivity of SV40 deoxyribonucleic acid with diethyl-amino-methyl-dextran.J. Natl. Cancer Inst. 41, 351–357.Google Scholar
  67. Miller A. D., Jolly D. J., Friedmann T., and Verya J. M. (1983), A transmissible retrovirus expressing human HPRT: Gene transfer into cells obtained from humans deficient in HPRT.Proc. Natl. Acad. Sci. USA 80, 4709–4713.PubMedCrossRefGoogle Scholar
  68. Miller A. D., Eckner R. J., Jolly D. J., Friedmann T., and Verma J. M. (1984a), Expression of a retrovirus encoding human HPRT in mice.Science 225, 630–632.PubMedCrossRefGoogle Scholar
  69. Miller A. D., Ong E. S., Rosenfeld M. G., Verma I. M., and Evams R. M. (1984), Infectious and selectable retrovirus containing an inducible rat growth hormone minigene.Science 225, 993–997.PubMedCrossRefGoogle Scholar
  70. Miller A. D., Law M. F., and Verma I. M. (1985), Generation of helper-free amphotropic retrovirus that transduce a dominant-acting, methotrexate-resistant dihydrofolate reductase gene.Mol. Cell. Biol. 5, 431–437.PubMedGoogle Scholar
  71. Morgan J. R., Barrandon Y., Green H., and Mulligan R. C. (1987), Expression of an exogenous growth hormone gene by transplantable human epidermal cells.Science 237, 1476–1479.PubMedCrossRefGoogle Scholar
  72. Mushinski J. F., Potter M., Bauer S. R., and Reddy E. R. (1983), DNA rearrangement and altered RNA expression of the c-myb oncogene in mouse plasma cytoid lymphosarcomas.Science 220, 795–798.PubMedCrossRefGoogle Scholar
  73. Neumann E., Schaefer-Ridder M., Wang Y., and Hofschneider P. H. (1982), Gene transfer into mouse lyoma cells by electroporotion in high electric fields.EMBO J. 1, 841–845.PubMedGoogle Scholar
  74. Noori-Daloii M. R., Swift R. A., Kung H.-J., Crittenden L. B., and Winter R. L. (1981), Specific integration of RSV proviruses in avian bursal lymphomas.Nature 294, 575–576.CrossRefGoogle Scholar
  75. Nusse R. and Varmus H. E. (1982), Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome.Cell 31, 99–109.PubMedCrossRefGoogle Scholar
  76. Nusse R., van Ooyen A., Cox D., Fung Y. K., and Varmus H. E. (1984), Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15.Nature 307, 131–136.PubMedCrossRefGoogle Scholar
  77. Payne G. S., Bishop J. M., and Varmus H. E. (1982), Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas.Nature 295, 209–213.PubMedCrossRefGoogle Scholar
  78. Peters G., Brooker S., Smith R., and Dickson C. (1983), Tumorigenesis by mouse mammary tumor virus: Evidence for a common region for provirus integration in mammary tumors.Cell 33, 369–377.PubMedCrossRefGoogle Scholar
  79. Price J., Turner D., and Cepko C. (1987), Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer.Proc. Natl. Acad. Sci. USA 84, 156–160.PubMedCrossRefGoogle Scholar
  80. Rechavi G., Givol D., and Canaani E. (1982), Activation of a cellular oncogene by DNA rearrangement: Possible involvement of an IS like element.Nature 300, 607–610.PubMedCrossRefGoogle Scholar
  81. Rohdewohld H., Weiher H., Reik W., Jaenisch R., and Breindl M. (1987), Retrovirus integration and chromatin structure: Moloney murine leukemia proviral integration sites map near DNase I-hypersensitive sites.J. Virol. 61, 336–343.PubMedGoogle Scholar
  82. Sandri-Goldin R. M., Goldin A. L., Levine M., and Glorioso J. C. (1981), High-frequency transfer of cloned Herpes simplex virus type 1 sequences to mammalian cells by protoplast fusion.Mol. Cell. Biol. 1, 743–752.PubMedGoogle Scholar
  83. Sanes J. R., Rubenstein L. R., and Nicolas J. F. (1986), Use of recombinant retrovirus to study post-implantation cell lineage in mouse embryos.EMBO J. 5, 3133–3142.PubMedGoogle Scholar
  84. Schnieke A., Stulmann H., Harbers K., Chumakoo I., and Jaenisch R. (1983), Endogenous Moloney leukemia virus in nonviremic MOV substrains of mice carries defects in the proviral genome.J. Virol. 45, 505–513.PubMedGoogle Scholar
  85. Schubach W. and Groudine M. (1984), Alteration of c-myc chromative structure by avian leukosis virus integration.Nature 307, 702–708.PubMedCrossRefGoogle Scholar
  86. Shiba T. and Saigo K. (1983), Retrovirus-like particles containing RNA homologous to the transposable element copia in Drosophil melanogaster.Nature 302, 119–123.PubMedCrossRefGoogle Scholar
  87. Shimotohno K. and Temin H. M. (1980), No apparent nucleotide sequence specificity in cellular DNA juxtaposed to retrovirus proviruses.Proc. Natl. Acad. Sci. USA 77, 7357–7361.PubMedCrossRefGoogle Scholar
  88. Shimotohno K., and Temin H. M. (1981), Formation of infectious progeny virus after insertion of herpes simplex thymidine kinase gene into DNA of an avian retrovirus.Cell 26, 67–77.PubMedCrossRefGoogle Scholar
  89. Sleckman B. P., Peterson A., Jones W. K., Foran J. A., Greenstein J. L., Seed B., and Burakoff S. J. (1987), Expression and function of CD4 in a murine T-cell hybridoma.Nature 328, 351–353.PubMedCrossRefGoogle Scholar
  90. Snyder S. H., and D’Amato R. J. (1986), MPTP: A neurotoxin relevant to the pathophysiology of Parkinson’s disease.Neurology 36, 250–258.PubMedGoogle Scholar
  91. Soriano P., Cone R. D., Mulligan R. C., and Jaenisch R. (1986), Tissue-specific and ectopic expression of genes introduced into transgenic mice by retroviruses.Science 234, 1409–1413.PubMedCrossRefGoogle Scholar
  92. Stevens J. R., Langloss J. M., Albrecht P., Yolken R., and Wang Y. N. (1984), A search for cytomegalovirus and herpes viral antigen in brains of schizophrenic patients.Arch. Gen. Psychiatry 41, 795–801.PubMedGoogle Scholar
  93. Stuhlmann H., Cone R., Mulligan R. C., and Jaenisch R. (1984), Introduction of a selectable gene into different animal tissue by a retrovirus recombinant vector.Proc. Natl. Acad. Sci. USA 81, 7151–7155.PubMedCrossRefGoogle Scholar
  94. Tabin C. J., Hoffman J. W., Goff S. P., and Weinberg R. A. (1982), Adaptation of a retrovirus as a eucaryotic vector transmitting the herpes simplex virus thymidine kinase gene.Mol. Cell. Biol. 4, 426–436.Google Scholar
  95. Teich N. (1984), Taxonomy of retrovirus,RNA Tumor Virus, Weiss, R., Teich, N., Varmus, H., and Coffin, J., eds., Cold Spring Harbor Laboratory, New York, pp. 25–207.Google Scholar
  96. Teich N., Wyke J., Mak T., Berstein A., and Hardy W. (1984), Pathogenesis of retrovirus-induced disease,RNA Tumor Virus, Weiss, R., Teich, N., Varmus, H., and Coffin, J., eds., Cold Spring Harbor Laboratory, New York, pp. 785–998.Google Scholar
  97. Teich N., Wyke J., and Kaplan P. (1985), Pathogenesis of retrovirus-induced disease,RNA Tumor Virus, Weiss, R., Teich, N., Varmus, H., and Coffin, J., eds., Cold Spring Harbor Laboratory, New York, pp. 187–248.Google Scholar
  98. Torrey E. F., and Peterson M. R. (1976), The viral hypothesis of schizophrenia.Schizophr. Bull. 2, 136–146.PubMedGoogle Scholar
  99. Tsichlis P. N., Hu L. F., and Strauss P. G. (1983a) Two common regions for proviral DNA integration in MoMuLV-induced rat thymic lymphomas impliations for oncogenesis,ICN-UCLA Symposium on Normal and Neoplastic Hematopoiesis, Golde D. W., Marks P. A. eds., A. R. Liss, New York, pp. 399–416.Google Scholar
  100. Tsichlis P. N., Strauss P. G., and Hu L. F. (1983b), A common region for proviral DNA integration in MoMuLV-induced rat thymic lymphomas.Nature 302, 445–448.PubMedCrossRefGoogle Scholar
  101. Turner D. L., and Cepko C. L. (1987), A common progenitoz for neurons and glie persists in rat retins late in development.Nature 328, 131–136.PubMedCrossRefGoogle Scholar
  102. Van der Putten H., Quint W., Verma I., and Berns A. (1982), Moloney murine leukemia virus induced tumors: recombinant provirus in active chromatin regions.Nucleic Acids Res. 10, 577–592.PubMedCrossRefGoogle Scholar
  103. Van der Putten H., Botteri F. M., Miller A. D., Rosenfeld M. G., Fan H., Evans R. M., and Verma I. M. (1985), Efficient insertion of genes into Varmus H. E., Quintrell N., and Ortiz S. (1981), Retroviruses as mutagens: Insertion and excision of a nontransforming provirus alter expression of a resident trans forming provirus.Cell 25, 23–36.Google Scholar
  104. Varmus H. E. (1982), Form and function of retroviral proviruses.Science 216, 812–820.PubMedCrossRefGoogle Scholar
  105. Varmus H. and Swanstrom R. (1985), Replication of Retroviruses,RNA Tumor Viruses, Weiss R., Teich N., Varmus H., and Coffin J., eds., Cold Spring Harbor Laboratory, New York, pp. 75–134.Google Scholar
  106. Watanabe S. and Temin H. M. (1982), Encapsidation sequences for spleen necrosis virus, an avian retrovirus, are between the 5′ long terminal repeat and the start of thegag gene.Proc. Natl. Acad. Sci. USA 79, 5986–5990.PubMedCrossRefGoogle Scholar
  107. Wei C., Gibson M., Spear P. G., and Scolnick E. M. (1981), Construction and isolation of a transmissible retrovirus containing thesrc gene of Harvey murine sarcoma virus and the thy midine kinase gene of herpes simplex virus type 1.J. Virol. 39, 935–944.PubMedGoogle Scholar
  108. Weinberger D. R., Wagner R. L., and Wyatt R. J. (1983), Neuropathological studies of schizophrenia: A selective review.Schizophr. Bull. 9, 193–212.PubMedGoogle Scholar
  109. Weintraub H. (1985), Assembly and propagation of repressed and derepressed chromatin states.Cell 42, 705–711.PubMedCrossRefGoogle Scholar
  110. Wiberg F. C., Sunnerhagen P., Kaltoft K., Zeuthen J., and Bjursell G. (1983), Replication and expression in mammalian cells of transfected DNA: description of an improved erythrocyte ghost fusion technique.Nucleic Acids Res. 11, 7287–7302.PubMedCrossRefGoogle Scholar
  111. Wigler M., Silverstein S., Lee L., Pellicer A., Chen V., Axel R. (1977), Transfer of the purified herpes virus thymidine kinase gene to cultured mouse cells.Cell 11, 223–232.PubMedCrossRefGoogle Scholar
  112. Williams D. A., Lemischka I. R., Nathan D. G., and Mulligan R. C. (1984), Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse.Nature 310, 476–480.PubMedCrossRefGoogle Scholar
  113. Wolf D., and Rotter V. (1984), Inactivation of p53 gene expression by an insertion of Moloney murine leukemia virus like sequence.Mol. Cell. Biol. 4, 1402–1410.PubMedGoogle Scholar
  114. Ymer S., Tucker W. Q. J., Sanderson C. J., Hapel A. J., Campbell H. D., and Young I. G. (1985), Constitutive synthesis of interleukin-3 by leukemia cell line WEJI-3B is due to retroviral insertion near the gene.Nature 317, 255–258.PubMedCrossRefGoogle Scholar
  115. Yu S. F., Von Ruden T., Kantoff P. W., Garber C., Sieberg M., Ruther U., Anderson E., Wagner E., and Gilboa E. (1986), Self inactivating retroviral vectors designed for transfer of whole genes into mammalian cells.Proc. Natl. Acad. Sci. USA 83, 3194–3198.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1988

Authors and Affiliations

  • Mathew M. S. Lo
    • 1
  • Mary K. Conrad
    • 1
  • Cleanthi Mamalaki
    • 1
  • Michael J. Kadan
    • 1
  1. 1.Molecular Biology and Genetics Unit, Neuroscience BranchNIDA, Addiction Research CenterBaltimore

Personalised recommendations