Sensory but not motor neuron deficits in mice lacking NT4 and BDNF

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Abstract

NEUROTROPHINS play important roles in neuronal survival during vertebrate development1–3. Neurotrophin-4 (NT4), alone or in combination with brain-derived neurotrophic factor (BDNF), has been suggested to be necessary for the survival of peripheral sensory neurons and central nervous system (CNS) neurons, including motor neurons4–16. To define the role of NT4 in vivo, we generated mice lacking NT4 by gene targeting. NT4-deficient mice were viable but exhibited a loss of sensory neurons in the nodose-petro-sal and geniculate ganglia. In contrast, motor neurons of the facial nucleus and sympathetic neurons of the superior cervical ganglion were unaffected, and there was no obvious loss of dopaminergic neurons in the substantia nigra. In mice lacking both NT4 and BDNF14,15, facial motor neurons remained unaffected, whereas the loss of sensory neurons was more severe than with either mutation alone. Thus NT4 is required during development for the survival of some peripheral sensory neurons but not sympathetic or motor neurons.

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References

  1. 1

    Levi-Montalcini, R. Science 237, 1154–1162 (1987).

  2. 2

    Barde, Y. A. Neuron 2, 1525–1534 (1989).

  3. 3

    Snider, W. D. Cell 77, 627–638 (1994).

  4. 4

    Berkemeier, L. R. et al. Neuron 7, 857–866 (1991).

  5. 5

    Hallbook, F., Ibanez, C. F. & Persson, H. Neuron 6, 845–858 (1991).

  6. 6

    Ip, N. Y. et al. Proc. natn. Acad. Sci. U.S.A. 89, 3060–3064 (1992).

  7. 7

    Timmusk, T., Belluardo, N., Metsis, M. & Persson, H. Eur. J. Neurosci. 5, 605–613 (1993).

  8. 8

    Klein, R., Lamballe, F., Bryant, S. & Barbacid, M. Neuron 8, 947–956 (1992).

  9. 9

    Davies, A. M. et al. J. Neurosci. 13, 4961–4967 (1993).

  10. 10

    Ibanez, C. F. et al. Development 117, 1345–1353 (1993).

  11. 11

    Fischer, W., Sirevaag, A., Wiegand, S. J., Lindsay, R. M. & Bjorklund, A. Proc. natn. Acad. Sci. USA. 91, 8607–8611 (1994).

  12. 12

    Hyman, C. et al. J. Neurosci. 14, 335–347 (1994).

  13. 13

    Koliatsos, V. E. et al. Proc. natn. Acad. Sci. U.S.A. 91, 3304–3308 (1994).

  14. 14

    Ernfors, P., Lee, K. F. & Jaenisch, R. Nature 368, 147–150 (1994).

  15. 15

    Jones, K. R., Farinas, I., Backus, C. & Reichardt, L. F. Cell 76, 989–999 (1994).

  16. 16

    Klein, R. et al. Cell 75, 113–122 (1993).

  17. 17

    Ip, N. Y. & Yancopoulos, G. D. Ann. Neurol. 35, S13–16 (1994).

  18. 18

    Klein, R., Conway, D., Parada, L. F. & Barbacid, M. Cell 61, 647–656 (1990).

  19. 19

    Middlemas, D. S., Lindberg, R. A. & Hunter, T. Molec. cell. Biol. 11, 143–153 (1991).

  20. 20

    Ernfors, P., Lee, K. F., Kucera, J. & Jaenisch, R. Cell 77, 503–512 (1994).

  21. 21

    Farinas, I., Jones, K. R., Backus, C., Wang, X. Y. & Reichardt, L. F. Nature 369, 658–661 (1994).

  22. 22

    Buchman, V. L. & Davies, A. M. Development 118, 989–1001 (1993).

  23. 23

    Di Cicco-Bloom, E., Friedman, W. J. & Black, I. B. Neuron 11, 1101–1111 (1993).

  24. 24

    Henderson, C. E. et al. Science 266, 1062–1064 (1994).

  25. 25

    Tomac, A. et al. Nature 373, 335–339 (1995).

  26. 26

    Beck, K. D. et al. Nature 373, 339–341 (1995).

  27. 27

    Yan, Q., Matheson, C. & Lopez, O. T. Nature 373, 341–344 (1995).

  28. 28

    Oppenheim, R. W. et al. Nature 373, 344–347 (1995).

  29. 29

    Li, E., Bestor, T. H. & Jaenisch, R. Cell 69, 915–926 (1992).

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Liu, X., Ernfors, P., Wu, H. et al. Sensory but not motor neuron deficits in mice lacking NT4 and BDNF. Nature 375, 238–241 (1995) doi:10.1038/375238a0

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