Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Oct 15;93(21):11974–11979. doi: 10.1073/pnas.93.21.11974

Adenovirus-mediated gene delivery into neuronal precursors of the adult mouse brain.

S O Yoon 1, C Lois 1, M Alvirez 1, A Alvarez-Buylla 1, E Falck-Pedersen 1, M V Chao 1
PMCID: PMC38168  PMID: 8876247

Abstract

Precursor cells found in the subventricular zone (SVZ) of the adult brain can undergo cell division and migrate long distances before differentiating into mature neurons. We have investigated the possibility of introducing genes stably into this population of cells. Replication-defective adenoviruses were injected into the SVZ of the lateral ventricle of adult mice. The adenoviruses carried a cDNA for the LacZ reporter or the human p75 neurotrophin receptor, for which species-specific antibodies are available. Injection of the viruses into the SVZ led to efficient labeling of neuronal precursors. Two months after viral injection, infected cells were detected in the olfactory bulb, a significant distance from the site of injection. Labeled periglomerular and granular neurons with extensive dendritic arborization were found in the olfactory bulb. These results demonstrate that foreign genes can be efficiently introduced into neuronal precursor cells. Furthermore, adenovirus-directed infection can lead to long-term stable gene expression in progenitor cells found in the adult central nervous system.

Full text

PDF
11974

Images in this article

Selected References

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

  1. Akli S., Caillaud C., Vigne E., Stratford-Perricaudet L. D., Poenaru L., Perricaudet M., Kahn A., Peschanski M. R. Transfer of a foreign gene into the brain using adenovirus vectors. Nat Genet. 1993 Mar;3(3):224–228. doi: 10.1038/ng0393-224. [DOI] [PubMed] [Google Scholar]
  2. Alvarez-Buylla A., Lois C. Neuronal stem cells in the brain of adult vertebrates. Stem Cells. 1995 May;13(3):263–272. doi: 10.1002/stem.5530130307. [DOI] [PubMed] [Google Scholar]
  3. Anton E. S., Weskamp G., Reichardt L. F., Matthew W. D. Nerve growth factor and its low-affinity receptor promote Schwann cell migration. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2795–2799. doi: 10.1073/pnas.91.7.2795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bajocchi G., Feldman S. H., Crystal R. G., Mastrangeli A. Direct in vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors. Nat Genet. 1993 Mar;3(3):229–234. doi: 10.1038/ng0393-229. [DOI] [PubMed] [Google Scholar]
  5. Barker P. A., Shooter E. M. Disruption of NGF binding to the low affinity neurotrophin receptor p75LNTR reduces NGF binding to TrkA on PC12 cells. Neuron. 1994 Jul;13(1):203–215. doi: 10.1016/0896-6273(94)90470-7. [DOI] [PubMed] [Google Scholar]
  6. Bayer S. A. Neurogenesis in the rat primary olfactory cortex. Int J Dev Neurosci. 1986;4(3):251–271. doi: 10.1016/0736-5748(86)90063-8. [DOI] [PubMed] [Google Scholar]
  7. Carter B. D., Kaltschmidt C., Kaltschmidt B., Offenhäuser N., Böhm-Matthaei R., Baeuerle P. A., Barde Y. A. Selective activation of NF-kappa B by nerve growth factor through the neurotrophin receptor p75. Science. 1996 Apr 26;272(5261):542–545. doi: 10.1126/science.272.5261.542. [DOI] [PubMed] [Google Scholar]
  8. Chao M. V. The p75 neurotrophin receptor. J Neurobiol. 1994 Nov;25(11):1373–1385. doi: 10.1002/neu.480251106. [DOI] [PubMed] [Google Scholar]
  9. Dobrowsky R. T., Werner M. H., Castellino A. M., Chao M. V., Hannun Y. A. Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor. Science. 1994 Sep 9;265(5178):1596–1599. doi: 10.1126/science.8079174. [DOI] [PubMed] [Google Scholar]
  10. Hempstead B. L., Schleifer L. S., Chao M. V. Expression of functional nerve growth factor receptors after gene transfer. Science. 1989 Jan 20;243(4889):373–375. doi: 10.1126/science.2536190. [DOI] [PubMed] [Google Scholar]
  11. Hersh J., Crystal R. G., Bewig B. Modulation of gene expression after replication-deficient, recombinant adenovirus-mediated gene transfer by the product of a second adenovirus vector. Gene Ther. 1995 Mar;2(2):124–131. [PubMed] [Google Scholar]
  12. Huber L. J., Chao M. V. Mesenchymal and neuronal cell expression of the p75 neurotrophin receptor gene occur by different mechanisms. Dev Biol. 1995 Jan;167(1):227–238. doi: 10.1006/dbio.1995.1019. [DOI] [PubMed] [Google Scholar]
  13. Johnson D., Lanahan A., Buck C. R., Sehgal A., Morgan C., Mercer E., Bothwell M., Chao M. Expression and structure of the human NGF receptor. Cell. 1986 Nov 21;47(4):545–554. doi: 10.1016/0092-8674(86)90619-7. [DOI] [PubMed] [Google Scholar]
  14. Kaplan M. S., McNelly N. A., Hinds J. W. Population dynamics of adult-formed granule neurons of the rat olfactory bulb. J Comp Neurol. 1985 Sep 1;239(1):117–125. doi: 10.1002/cne.902390110. [DOI] [PubMed] [Google Scholar]
  15. Kass-Eisler A., Falck-Pedersen E., Alvira M., Rivera J., Buttrick P. M., Wittenberg B. A., Cipriani L., Leinwand L. A. Quantitative determination of adenovirus-mediated gene delivery to rat cardiac myocytes in vitro and in vivo. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11498–11502. doi: 10.1073/pnas.90.24.11498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Le Gal La Salle G., Robert J. J., Berrard S., Ridoux V., Stratford-Perricaudet L. D., Perricaudet M., Mallet J. An adenovirus vector for gene transfer into neurons and glia in the brain. Science. 1993 Feb 12;259(5097):988–990. doi: 10.1126/science.8382374. [DOI] [PubMed] [Google Scholar]
  17. Levison S. W., Chuang C., Abramson B. J., Goldman J. E. The migrational patterns and developmental fates of glial precursors in the rat subventricular zone are temporally regulated. Development. 1993 Nov;119(3):611–622. doi: 10.1242/dev.119.3.611. [DOI] [PubMed] [Google Scholar]
  18. Lois C., Alvarez-Buylla A. Long-distance neuronal migration in the adult mammalian brain. Science. 1994 May 20;264(5162):1145–1148. doi: 10.1126/science.8178174. [DOI] [PubMed] [Google Scholar]
  19. Lois C., Alvarez-Buylla A. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2074–2077. doi: 10.1073/pnas.90.5.2074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Luskin M. B. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron. 1993 Jul;11(1):173–189. doi: 10.1016/0896-6273(93)90281-u. [DOI] [PubMed] [Google Scholar]
  21. Mahadeo D., Kaplan L., Chao M. V., Hempstead B. L. High affinity nerve growth factor binding displays a faster rate of association than p140trk binding. Implications for multi-subunit polypeptide receptors. J Biol Chem. 1994 Mar 4;269(9):6884–6891. [PubMed] [Google Scholar]
  22. Morshead C. M., Reynolds B. A., Craig C. G., McBurney M. W., Staines W. A., Morassutti D., Weiss S., van der Kooy D. Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron. 1994 Nov;13(5):1071–1082. doi: 10.1016/0896-6273(94)90046-9. [DOI] [PubMed] [Google Scholar]
  23. Patil N., Lacy E., Chao M. V. Specific neuronal expression of human NGF receptors in the basal forebrain and cerebellum of transgenic mice. Neuron. 1990 Mar;4(3):437–447. doi: 10.1016/0896-6273(90)90056-l. [DOI] [PubMed] [Google Scholar]
  24. Rabizadeh S., Oh J., Zhong L. T., Yang J., Bitler C. M., Butcher L. L., Bredesen D. E. Induction of apoptosis by the low-affinity NGF receptor. Science. 1993 Jul 16;261(5119):345–348. doi: 10.1126/science.8332899. [DOI] [PubMed] [Google Scholar]
  25. Reynolds B. A., Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992 Mar 27;255(5052):1707–1710. doi: 10.1126/science.1553558. [DOI] [PubMed] [Google Scholar]
  26. Richards L. J., Kilpatrick T. J., Bartlett P. F. De novo generation of neuronal cells from the adult mouse brain. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8591–8595. doi: 10.1073/pnas.89.18.8591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ross A. H., Grob P., Bothwell M., Elder D. E., Ernst C. S., Marano N., Ghrist B. F., Slemp C. C., Herlyn M., Atkinson B. Characterization of nerve growth factor receptor in neural crest tumors using monoclonal antibodies. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6681–6685. doi: 10.1073/pnas.81.21.6681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Taniuchi M., Johnson E. M., Jr Characterization of the binding properties and retrograde axonal transport of a monoclonal antibody directed against the rat nerve growth factor receptor. J Cell Biol. 1985 Sep;101(3):1100–1106. doi: 10.1083/jcb.101.3.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Verdi J. M., Birren S. J., Ibáez C. F., Persson H., Kaplan D. R., Benedetti M., Chao M. V., Anderson D. J. p75LNGFR regulates Trk signal transduction and NGF-induced neuronal differentiation in MAH cells. Neuron. 1994 Apr;12(4):733–745. doi: 10.1016/0896-6273(94)90327-1. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES