Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4

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Abstract

NERVE growth factor and other neurotrophins signal to neurons through the Trk family of receptor tyrosine kinases1–6. TrkB is relatively promiscuous in vitro, acting as a receptor for brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT4) and, to a lesser extent, NT3 (refs 3–5). Mice lacking TrkB7 show a more severe phenotype than mice lacking BDNF8,9, suggesting that TrkB may act as a receptor for additional ligands in vivo. To explore this possibility, we generated mice lacking NT4 or BDNF as well as mice lacking both neurotrophins. Unlike mice lacking other Trks7,10,11 or neurotrophins8,9,12–14, NT4-deficient mice are long-lived and show no obvious neurological defects. Analysis of mutant phenotypes revealed distinct neuronal populations with different neurotrophin requirements. Thus vestibular and trigemi-nal sensory neurons require BDNF but not NT4, whereas nodose-petrosal sensory neurons require both BDNF and NT4. Motor neurons, whose numbers are drastically reduced in mice lacking TrkB, are not affected even in mice lacking both BDNF and NT4. These results suggest that another ligand, perhaps NT3, does indeed act on TrkB in vivo.

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References

  1. 1

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

  2. 2

    Eide, F. F., Lowenstein, D. H. & Reichardt, L. F. Expl Neurol. 121, 200–214 (1993).

  3. 3

    Glass, D. J. & Yancopoulos, G. D. Trends Cell Biol. 3, 262–268 (1993).

  4. 4

    Barbacid, M. J. Neurobiol. 25, 1386–1403 (1994).

  5. 5

    Ip, N. Y. et al. Neuron 10, 137–149 (1993).

  6. 6

    Davies, A. M. J. Neurobiol. 25, 1334–1348 (1994).

  7. 7

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

  8. 8

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

  9. 9

    Jones, K. R. Fariñas, I., Backus, C. & Reichardt, L. F. Cell 76, 989–1000 (1994).

  10. 10

    Smeyne R. J. et al. Nature 368, 246–249 (1994).

  11. 11

    Klein, R. et al. Nature 368, 249–251 (1994).

  12. 12

    Crowley, C. et al. Cell 76, 1001–1011 (1994).

  13. 13

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

  14. 14

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

  15. 15

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

  16. 16

    Yan, Q., Elliott, J., & Snider, W. D. Nature 360, 753–755 (1992).

  17. 17

    Oppenheim, R. W., Qin-Wei, Y., Prevette, D. & Yan, Q. Nature 360, 755–757 (1992).

  18. 18

    Sendtner, M., Holtmann, B., Kolbeck, R., Thoenen, H. & Barde, Y.-A. Nature 360, 757–758 (1992).

  19. 19

    Henderson, C. E. et al. Nature 363, 266–270 (1993).

  20. 20

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

  21. 21

    Li, L., Oppenheim, R. W., Lei, M. & Houenou, L. J. J. Neurobiol. 15, 759–766 (1994).

  22. 22

    Vejsada, R., Sagot, Y. & Kato, A. C. Eur. J. Neurosci. 7, 108–115 (1995).

  23. 23

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

  24. 24

    Thaler, C. D., Suhr, L., Ip, N. Y. & Katz, D. M. Devl Biol. 161, 338–344 (1994).

  25. 25

    Hertzberg, T., Fan, G., Finley, J. C., Erickson, J. T. & Katz, D. M. Devl Biol. 166, 801–811 (1994).

  26. 26

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

  27. 27

    Maisonpierre, P. C. et al. Neuron 5, 501–509 (1990).

  28. 28

    Squinto, S. P. et al. Cell 65, 885–893 (1991).

  29. 29

    Pover, C. M. & Coggeshall, R. E. Anat. Rec. 231, 573–578 (1991).

  30. 30

    Abercrombie, E. M. Anat. Rec. 94, 239–247 (1946).

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Conover, J., Erickson, J., Katz, D. et al. Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature 375, 235–238 (1995) doi:10.1038/375235a0

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