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Disruption of the CNTF gene results in motor neuron degeneration

Abstract

CNTF is a cytosolic molecule expressed postnatally in myelinating Schwann cells and in a sub-population of astrocytes. Although CNTF administration prevents lesion-mediated and genetically determined motor neuron degeneration, its physiological function remained elusive. Here it is reported that abolition of CNTF gene expression by homologous recombination results in a progressive atrophy and loss of motor neurons in adult mice, which is functionally reflected by a small but significant reduction in muscle strength.

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References

  1. Barbin, G., Manthorpe, M. & Varon, S. J. Neurochem. 43, 1468–1478 (1984).

    Article  CAS  Google Scholar 

  2. Sendtner, M., Arakawa, Y., Stöckli, K. A., Kreutzberg, G. W. & Thoenen, H. J. Cell Sci. 15, (suppl.), 103–109 (1991).

    Article  CAS  Google Scholar 

  3. Arakawa, Y., Sendtner, M. & Thoenen, H. J. Neurosci. 10, 3507–3515 (1990).

    Article  CAS  Google Scholar 

  4. Magal, E., Burnham, P. & Varon, S. Devl Brain Res. 63, 141–150 (1991).

    Article  CAS  Google Scholar 

  5. Ip, N. Y. et al. J. Neurosci. 11, 3124–3134 (1991).

    Article  CAS  Google Scholar 

  6. Saadat, S., Sendtner, M. & Rohrer, H. J. Cell Biol. 108, 1807–1816 (1989).

    Article  CAS  Google Scholar 

  7. Louis, J. C., Magal, E., Takayama, S. & Varon, S. Science 259, 689–692 (1993).

    Article  ADS  CAS  Google Scholar 

  8. Lillien, L. E. & Raff, M. C. Neuron 5, 111–119 (1990).

    Article  CAS  Google Scholar 

  9. Sendtner, M., Kreutzberg, G. W. & Thoenen, H. Nature 345, 440–441 (1990).

    Article  ADS  CAS  Google Scholar 

  10. Sendtner, M. et al. Nature 358, 502–504 (1992).

    Article  ADS  CAS  Google Scholar 

  11. Stöckli, K. A. et al. J. Cell Biol. 115, 447–459 (1991).

    Article  Google Scholar 

  12. Lin, L.-F. H. et al. Science 246, 1023–1025 (1989).

    Article  ADS  CAS  Google Scholar 

  13. Stöckli, K. A. et al. Nature 342, 920–923 (1989).

    Article  ADS  Google Scholar 

  14. Dobrea, G. M., Unnerstall, J. R. & Rao, M. S. Devl Brain Res. 66, 209–219 (1992).

    Article  CAS  Google Scholar 

  15. Lillien, L. E., Sendtner, M., Rohrer, H., Hughes, S. M. & Raff, M. C. Neuron 1, 485–494 (1988).

    Article  CAS  Google Scholar 

  16. Oppenheim, R. W. J. comp. Neurol. 246, 281–286 (1986).

    Article  CAS  Google Scholar 

  17. Mignatti, P., Morimoto, T. & Rifkin, D. B. J. Cell Physiol. 151, 81–93 (1992).

    Article  CAS  Google Scholar 

  18. Kandel, J. et al. Cell 66, 1095–1104 (1991).

    Article  CAS  Google Scholar 

  19. Sendtner, M., Stöckli, K. A. & Thoenen, H. J. Cell Biol. 188, 139–148 (1992).

    Article  Google Scholar 

  20. Bradley, A. in Teratocarcinomas and Embryonic Stem Cells (ed. Robertson, E. J.) 113–151 (IRL, Oxford, Washington DC, 1987).

    Google Scholar 

  21. Capecchi, M. R. Science 244, 1288–1292 (1989).

    Article  ADS  CAS  Google Scholar 

  22. Doetschman, T., Eistetter, H., Katz, M., Schmidt, W. & Kemler, R. J. Embryol. exp Morphol 87, 27–85 (1985).

    CAS  PubMed  Google Scholar 

  23. Wolf, E., Masu, Y., Thoenen, H. & Brem, G. Theriogenology 37, 341 (1993).

    Article  Google Scholar 

  24. Streit, J. W. J. Histochem. Cytochem. 38, 1683–1686 (1990).

    Article  CAS  Google Scholar 

  25. Streit, J. W., Graeber, M. B. & Kreutzberg, G. W. Glia 1, 301–307 (1988).

    Article  CAS  Google Scholar 

  26. Tetzlaff, W., Graeber, M. B., Bisby, M. A. & Kreutzberg, G. Glia 1, 90–95 (1988).

    Article  CAS  Google Scholar 

  27. Cork, L. C. et al. Lab. Invest. 61, 69–76 (1989).

    CAS  PubMed  Google Scholar 

  28. Munsat, T. L., Andres, P. L., Finison, L., Conlon, T. & Thibodeau, L. Neurology 38, 409–413 (1988).

    Article  CAS  Google Scholar 

  29. Meyer, M., Matsuoka, I., Wetmore, C., Olsen, L. & Thoenen, H. J. Cell Biol. 119, 45–54 (1992).

    Article  CAS  Google Scholar 

  30. McNeil, P. L. & Ito, S. J. Cell Sci. 96, 549–556 (1990).

    CAS  PubMed  Google Scholar 

  31. Rao, M. S., Patterson, P. H. & Landis, S. C. Development 116, 731–744 (1992).

    CAS  PubMed  Google Scholar 

  32. Rao, M. S. & Landis, S. C. J. Neurobiol. 24, 215–232 (1993).

    Article  CAS  Google Scholar 

  33. Abercrombie, M. Anat. Rec. 54, 239–247 (1946).

    Article  Google Scholar 

  34. Meyer, O. A., Tilson, H. A., Byrd, W. C. & Riley, M. T. Neurobehav. Toxicol. 1, 233–236 (1973).

    Google Scholar 

  35. SAS/STATR User's Guide Version 6 4th edn. Vol. 2, 891–996 (SAS Institute Inc., Cary, NC, 1989).

  36. Ramirez-Solis, R. et al. Analyt. Biochem. 201, 331–335 (1992).

    Article  CAS  Google Scholar 

  37. Sabatini, D. R., Bensch, K. & Barnett, R. J. J. Cell Biol. 7, 19–58 (1963).

    Article  Google Scholar 

  38. Luft, J. H. J. biophys. biochem. Cytol. 9, 409–414 (1961).

    Article  CAS  Google Scholar 

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Masu, Y., Wolf, E., Holtmann, B. et al. Disruption of the CNTF gene results in motor neuron degeneration. Nature 365, 27–32 (1993). https://doi.org/10.1038/365027a0

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