Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4.
Nerve growth factor and other neurotrophins signal to neurons through the Trk family of receptor tyrosine kinases. 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 TrkB show a more severe phenotype than mice lacking BDNF, 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 Trks or neurotrophins, 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 trigeminal 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.
Conover
J C
JC
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
Erickson
J T
JT
Katz
D M
DM
Bianchi
L M
LM
Poueymirou
W T
WT
McClain
J
J
Pan
L
L
Helgren
M
M
Ip
N Y
NY
Boland
P
P
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D051379:Mice; D008807:Mice, Inbred BALB C; D009046:Motor Neurons / Q000502:physiology*; D016296:Mutagenesis; D009414:Nerve Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009422:Nervous System Diseases / Q000235:genetics / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000502:physiology*; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; C073922:neurotrophin 4