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Letters to Nature
Nature 375, 235 - 238 (18 May 1995); doi:10.1038/375235a0

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

J. C. Conover*, J. T. Erickson, D. M. Katz, L. M. Bianchi*, W. T. Poueymirou*, J. McClain*, L. Pan*, M. Helgren*, N. Y. Ip*, P. Boland*, B. Friedman*, S. Wiegand*, R. Vejsada, A. C. Kato, T. M. DeChiara* & G. D. Yancopoulos*

*Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
Department of Pharmacology & Division of Clinical Neuromuscular Research, University Medical Centre, Geneva, Switzerland

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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