Skip to main content

Construction and Analysis of Transgenic Animals Overexpressing Neurotrophins

  • Protocol
Neurotrophin Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 169))

  • 380 Accesses

Abstract

The ability to manipulate the mouse genome has provided extremely useful model systems for studying the underlying molecular mechanisms of neurotrophin peptide action in mammalian development and adult systems. One way to use transgenics is to overexpress neurotrophins in neuronal target tissues to investigate how target expression of neurotrophic factors affects neuronal development and function in the adult. This review presents the basic experimental design considerations of this approach and describes selected techniques used to evaluate transgenic phenotypes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Shelton, D. L. and Rheichardt, L. F. (1984) Expression of the beta-nerve growth factor gene correltes with the density of sympathetic innervation in effector organs. Proc. Natl. Acad. Sci. USA 81, 7951–7955.

    Article  PubMed  CAS  Google Scholar 

  2. Edwards, R. H., Rutter, W. J., and Hanahan, D. (1989) Directed expression of NGF to pancreatic beta cells in transgenic mice leads to selective hyperinnervation of the islets. Cell 58, 161–170.

    Article  PubMed  CAS  Google Scholar 

  3. Borrelli, E., Sawchenko, P. E., and Evans, R. M. (1992) Pituitary hyperplasia induced by ectopic expression of nerve growth factor. Proc. Natl. Acad. Sci. USA 89, 2764–2768.

    Article  PubMed  CAS  Google Scholar 

  4. Albers, K. M., Wright, D. E., and Davis, B. M.(1994) Overexpression of nerve growth factor in epidermis of transgenic mice causes hypertrophy of the peripheral nervous system. J. Neurosci. 14, 1422-1432.

    Google Scholar 

  5. Ma, W., Ribeiro-da-Silva, A., Noel, G., Julien, J. P., and Cuello, A. C. (1995) Ectopic substance P and calcitonin gene-related peptide immunoreactive fibres in the spinal cord of transgenic mice over-expressing nerve growth factor. Eur. J. Neurosci. 7, 2021–2035.

    Article  PubMed  CAS  Google Scholar 

  6. Hassankhani, A., Steinhelper, M. E., Soonpan, M. H., et al. (1995) Overexpression of NGF within the heart of transgenic mice causes hyperinnervation, cardiac enlargement, and hyperplasia of ectopic cells. Dev. Biol. 169, 309–321.

    Article  PubMed  CAS  Google Scholar 

  7. Kawaja, M. D. and Crutcher, K. A. (1997) Sympathetic acons invade the brains of mice overexpressing nerve growth factor. J. Comp. Neurol. 23, 60–72.

    Article  Google Scholar 

  8. Hoyle, G. W., Graham, R. M., Finkelstein, J. B., Nguyen, K. P., Gozal, D., and Friedman, M. (1998) Hyperinnervation of the airways in transgenic mice overexpressing nerve growth factor. Am. J. Respir. CellMol. Biol. 18, 149–157.

    CAS  Google Scholar 

  9. Gerlai, R. (1996) Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci. 19, 177–181.

    Article  PubMed  CAS  Google Scholar 

  10. Crawley, J. N. (1996) Unusual behavioral phenotypes of inbred mouse strains. Trends Neurosci. 19, 181,182.

    Article  Google Scholar 

  11. Hogan, B., Costantini, F., and Lacy, E. (1986) Manipulating the Mouse Embryo. A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.1

    Google Scholar 

  12. Silva, A. J. (1997) Banbury Conference on Genetic Background in Mice: mutant mice and neuroscience: recommendations concerning genetic background. Neuron 19, 755–759.

    Article  Google Scholar 

  13. Frankel, W. N. (1997) Mouse strain backgrounds: more than black and white. Neuron 20, 183.

    Article  Google Scholar 

  14. Brinster, R. L., Allen, J. M., Behringer, R. R., Gelinas, R. E., and Palmiter, R. D. (1988) Introns increase transcriptional efficiency in transgenic micex. Proc. Natl. Acad. Sci. USA 85, 836–840.

    Article  PubMed  CAS  Google Scholar 

  15. Abercrombie, M. (1946) Estimation of nuclear population from microtome sections. Anat. Rec. 94, 239–247.

    Article  PubMed  CAS  Google Scholar 

  16. Konigsmark, B. W. (1970) in Contemporary Research Methods in Neuroanatomy (Nauta, W. J. H. and Ebbesson, S. O. E., eds.), Springer-Verlag, NewYork, pp. 315–338.

    Google Scholar 

  17. Coggeshall, R. E. (1992) A consideration of counting methods. Trends Neurosci. 15, 9–13.

    Article  PubMed  CAS  Google Scholar 

  18. Sterio, D. C. (1984) The unbiased estimation of number and sizes of arbitrary particles using the dissector. J. Microsc. 134, 127–136.

    PubMed  CAS  Google Scholar 

  19. West, J. H. (1993) New steriological methods for counting neurons. Neurobiol.Aging 14, 275–285.

    Article  PubMed  CAS  Google Scholar 

  20. Pakkenberg, B. and Gundersen, H. J. (1997) Neocortical neuron number in humans: effect of sex and age. J. Comp. Neurol. 384, 312–320.

    Article  PubMed  CAS  Google Scholar 

  21. West, M. and Slomianka, L. (1998) Total number of neurons in the layers of the human entorhinal cortex. Hippocampus 8, 69–82.

    Article  PubMed  CAS  Google Scholar 

  22. Saper, C. B.(1996) Any way you cut it: a new journal policy for the use of unbiased counting methods. J. Comp. Neurol. 364, 5.

    Article  PubMed  CAS  Google Scholar 

  23. Guillery, R. W. and Herrup, K. (1997) Quantification without pontification: choosing a method for counting objects in sectioned tissue. J. Comp. Neurol. 368, 2–7.

    Article  Google Scholar 

  24. Popken, G. J. and Farel, P. B. (1997) Sensory neuron number in neonatal and adult rats estimated by means of stereological and profile-based method. J. Comp. Neurol. 386, 8–15.

    Article  PubMed  CAS  Google Scholar 

  25. Creedon, D. and Tuttle, J. B. (1991) Nerve growth factor synthesis in vascular smooth muscle. Hypertension 18, 730–741.

    PubMed  CAS  Google Scholar 

  26. Hogue-Angelett, R. (1969) Nerve growth factor (NGF) from snake venom and mouse maxillary gland: interactions with serum proteins. Brain Res. 12, 234–346.

    Article  Google Scholar 

  27. Koo, P. H. and Stach, P. W. (1989) Interaction of nerve growth factor with a-macroglobulin. J. Neurosci. Res. 22, 247–261.

    Article  PubMed  CAS  Google Scholar 

  28. Suda, K., Barde, Y. A., and Thoenen, H. (1978) Nerve growth factor in mouse and rat serum: correlation between bioassay and radioimmunoassay determinations. Proc. Natl. Acad. Sci. USA 75, 4042–4046.

    Article  PubMed  CAS  Google Scholar 

  29. Ronne, H., Anundi, H., Rask, L., and Peterson, P. A. (1979) Nerve growth binds to serum alpha-2-macroglobulin. Biochem. Biophys. Res. Commun. 87, 330–336.

    Article  PubMed  CAS  Google Scholar 

  30. Murase, K., Takeuchi, R., Iwata, E., Furukawa, Y., and Hayashi, K. (1992) Developmental changes in nerve growth factor level in rat serum. J. Neurosci. Res. 33, 282–288.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Humana Press Inc.

About this protocol

Cite this protocol

Albers, K.M., Davis, B.M. (2001). Construction and Analysis of Transgenic Animals Overexpressing Neurotrophins. In: Rush, R.A. (eds) Neurotrophin Protocols. Methods in Molecular Biology™, vol 169. Humana Press. https://doi.org/10.1385/1-59259-060-8:149

Download citation

  • DOI: https://doi.org/10.1385/1-59259-060-8:149

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-699-4

  • Online ISBN: 978-1-59259-060-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics