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Gene Review

Ntf3  -  neurotrophin 3

Mus musculus

Synonyms: AI316846, AI835689, HDNF, NGF-2, NT-3, ...
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Disease relevance of Ntf3


Psychiatry related information on Ntf3

  • As in NT3 and TrkC null mice, the proprioception system of these mutants failed to assemble [4].
  • Together, these findings demonstrate that NT-3 signaling counters Abeta-dependent neuronal cell death and may represent an innovative therapeutic intervention to limit neuronal death in Alzheimer disease [5].
  • Transgene-derived NT-3 expressed by noradrenergic neurons of conditional mutants restored opiate withdrawal symptoms [6].
  • Wild-type (n=12) and mlc/NT-3 (n=12) male mice were tested in five procedures (in chronological order): lick dynamics, locomotor activity, grid ataxia, go-no-go discrimination procedure, and grip strength [7].

High impact information on Ntf3

  • Interestingly, final target-derived NGF promotes expression of the p75 neurotrophin receptor, in turn causing a reduction in the sensitivity of axons to intermediate target-derived NT-3 [8].
  • We report that the related neurotrophins NGF and NT-3, acting through a common receptor, TrkA, are required for sequential stages of sympathetic axon growth and, thus, innervation of target fields [8].
  • The observed defects are consistent with abnormalities in the survival and/or migration of cardiac neural crest early in embryogenesis and establish an essential role for neurotrophin 3 in regulating the development of the mammalian heart [9].
  • Peripheral neuronal subpopulations expressing the TrkC receptor tyrosine kinase respond to Nt3 with enhanced survival, mitogenesis or cell migration and these neurons are lost in homozygous Nt3 null (-/-) mutant mice [9].
  • Histological and echocardiographic image analysis of Nt3-/- animals reveal severe cardiovascular abnormalities including atrial and ventricular septal defects, and tetralogy of Fallot, resembling some of the most common congenital malformations in humans [9].

Chemical compound and disease context of Ntf3


Biological context of Ntf3


Anatomical context of Ntf3


Associations of Ntf3 with chemical compounds


Physical interactions of Ntf3


Regulatory relationships of Ntf3

  • The p75 neurotrophin receptor influences NT-3 responsiveness of sympathetic neurons in vivo [26].
  • In primary striatal cultures, NT-3 treatment induced an enhancement in NR2A, but not NR2B, protein levels [20].
  • In conclusion, NT-3 regulates the expression of NMDAR subunits modifying striatal neuronal properties that confers the differential vulnerability to excitotoxicity in projection neurons and interneurons in the striatum [20].
  • Our results show that NT3 expressed emporally and spatially in the place of BDNF is sufficient in some neuronal populations to compensate for the loss of BDNF [27].
  • Here we provide evidence that both the mitogenic effect of bFGF and the differentiation-promoting effect of NT3 are linked with modifications of cell cycle kinetics in mouse cortical precursor cells [28].

Other interactions of Ntf3

  • In these assays, BDNF elicits a response at least two orders of magnitude higher than NT-3 [12].
  • Characterization of neurotrophin and Trk receptor functions in developing sensory ganglia: direct NT-3 activation of TrkB neurons in vivo [29].
  • Many, but not all, of the NT3- and NT4-dependent neurons switch to BDNF at later stages [30].
  • However, intrastriatal grafting of NT-3 secreting-cells in adult wild type mice produced a down-regulation of NR2A subunit [20].
  • This expression of p75NTR by epithelial target cells required NT-3 but not adult innervation [31].

Analytical, diagnostic and therapeutic context of Ntf3


  1. Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo evidence for NT-3 activation of TrkA and TrkB in addition to TrkC. Huang, E.J., Wilkinson, G.A., Fariñas, I., Backus, C., Zang, K., Wong, S.L., Reichardt, L.F. Development (1999) [Pubmed]
  2. Role of neurotrophins in mouse neuronal development. Klein, R. FASEB J. (1994) [Pubmed]
  3. Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose deprivation, and oxidative stress: possible involvement of oxygen free radicals. Bates, B., Hirt, L., Thomas, S.S., Akbarian, S., Le, D., Amin-Hanjani, S., Whalen, M., Jaenisch, R., Moskowitz, M.A. Neurobiol. Dis. (2002) [Pubmed]
  4. Dissection of NT3 functions in vivo by gene replacement strategy. Coppola, V., Kucera, J., Palko, M.E., Martinez-De Velasco, J., Lyons, W.E., Fritzsch, B., Tessarollo, L. Development (2001) [Pubmed]
  5. Akt-dependent expression of NAIP-1 protects neurons against amyloid-{beta} toxicity. Lesné, S., Gabriel, C., Nelson, D.A., White, E., Mackenzie, E.T., Vivien, D., Buisson, A. J. Biol. Chem. (2005) [Pubmed]
  6. Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal. Akbarian, S., Bates, B., Liu, R.J., Skirboll, S.L., Pejchal, T., Coppola, V., Sun, L.D., Fan, G., Kucera, J., Wilson, M.A., Tessarollo, L., Kosofsky, B.E., Taylor, J.R., Bothwell, M., Nestler, E.J., Aghajanian, G.K., Jaenisch, R. Mol. Psychiatry (2001) [Pubmed]
  7. Low grip strength, impaired tongue force and hyperactivity induced by overexpression of neurotrophin-3 in mouse skeletal muscle. Fowler, S.C., Zarcone, T.J., Chen, R., Taylor, M.D., Wright, D.E. Int. J. Dev. Neurosci. (2002) [Pubmed]
  8. A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling. Kuruvilla, R., Zweifel, L.S., Glebova, N.O., Lonze, B.E., Valdez, G., Ye, H., Ginty, D.D. Cell (2004) [Pubmed]
  9. Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development. Donovan, M.J., Hahn, R., Tessarollo, L., Hempstead, B.L. Nat. Genet. (1996) [Pubmed]
  10. Differential effects of TrkC isoforms on sensory axon outgrowth. Ichinose, T., Snider, W.D. J. Neurosci. Res. (2000) [Pubmed]
  11. Viral and non-viral gene therapy partially prevents experimental cisplatin-induced neuropathy. Pradat, P.F., Kennel, P., Naimi-Sadaoui, S., Finiels, F., Scherman, D., Orsini, C., Delaere, P., Mallet, J., Revah, F. Gene Ther. (2002) [Pubmed]
  12. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Klein, R., Nanduri, V., Jing, S.A., Lamballe, F., Tapley, P., Bryant, S., Cordon-Cardo, C., Jones, K.R., Reichardt, L.F., Barbacid, M. Cell (1991) [Pubmed]
  13. Neurotrophin-3 signaling in mammalian Merkel cell development. Szeder, V., Grim, M., Kucera, J., Sieber-Blum, M. Dev. Dyn. (2003) [Pubmed]
  14. Site-specific interactions of neurotrophin-3 and fibroblast growth factor (FGF2) in the embryonic development of the mouse cochlear nucleus. Hossain, W.A., D'Sa, C., Morest, D.K. J. Neurobiol. (2006) [Pubmed]
  15. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 act as "epitheliotrophins" in murine skin. Botchkarev, V.A., Metz, M., Botchkareva, N.V., Welker, P., Lommatzsch, M., Renz, H., Paus, R. Lab. Invest. (1999) [Pubmed]
  16. A disorganized innervation of the inner ear persists in the absence of ErbB2. Morris, J.K., Maklad, A., Hansen, L.A., Feng, F., Sorensen, C., Lee, K.F., Macklin, W.B., Fritzsch, B. Brain Res. (2006) [Pubmed]
  17. Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Ernfors, P., Lee, K.F., Kucera, J., Jaenisch, R. Cell (1994) [Pubmed]
  18. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Soppet, D., Escandon, E., Maragos, J., Middlemas, D.S., Reid, S.W., Blair, J., Burton, L.E., Stanton, B.R., Kaplan, D.R., Hunter, T. Cell (1991) [Pubmed]
  19. The role of neurotrophic factors in regulating the development of inner ear innervation. Fritzsch, B., Silos-Santiago, I., Bianchi, L.M., Fariñas, I. Trends Neurosci. (1997) [Pubmed]
  20. Mice heterozygous for neurotrophin-3 display enhanced vulnerability to excitotoxicity in the striatum through increased expression of N-methyl-d-aspartate receptors. Torres-Peraza, J., Pezzi, S., Canals, J.M., Gavald??, N., Garc??a-Mart??nez, J.M., P??rez-Navarro, E., Alberch, J. Neuroscience (2007) [Pubmed]
  21. The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3. Cordon-Cardo, C., Tapley, P., Jing, S.Q., Nanduri, V., O'Rourke, E., Lamballe, F., Kovary, K., Klein, R., Jones, K.R., Reichardt, L.F. Cell (1991) [Pubmed]
  22. Localization of nerve growth factor, neurotrophin-3, and glial cell line-derived neurotrophic factor in nestin-expressing reactive astrocytes in the caudate-putamen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/Bl mice. Chen, L.W., Zhang, J.P., Kwok-Yan Shum, D., Chan, Y.S. J. Comp. Neurol. (2006) [Pubmed]
  23. Levels of nerve growth factor and neurotrophin-3 are affected differentially by the presence of p75 in sympathetic neurons in vivo. Harrison, S.M., Jones, M.E., Uecker, S., Albers, K.M., Kudrycki, K.E., Davis, B.M. J. Comp. Neurol. (2000) [Pubmed]
  24. Analysis of mitogen-activated protein kinase activation by naturally occurring splice variants of TrkC, the receptor for neurotrophin-3. Gunn-Moore, F.J., Williams, A.G., Tavaré, J.M. Biochem. J. (1997) [Pubmed]
  25. MPTP-treated young mice but not aging mice show partial recovery of the nigrostriatal dopaminergic system by stereotaxic injection of acidic fibroblast growth factor (aFGF). Date, I., Notter, M.F., Felten, S.Y., Felten, D.L. Brain Res. (1990) [Pubmed]
  26. The p75 neurotrophin receptor influences NT-3 responsiveness of sympathetic neurons in vivo. Brennan, C., Rivas-Plata, K., Landis, S.C. Nat. Neurosci. (1999) [Pubmed]
  27. Differential influence of BDNF and NT3 on the expression of calcium binding proteins and neuropeptide Y in vivo. Agerman, K., Ernfors, P. Neuroreport (2003) [Pubmed]
  28. Contrasting effects of basic fibroblast growth factor and neurotrophin 3 on cell cycle kinetics of mouse cortical stem cells. Lukaszewicz, A., Savatier, P., Cortay, V., Kennedy, H., Dehay, C. J. Neurosci. (2002) [Pubmed]
  29. Characterization of neurotrophin and Trk receptor functions in developing sensory ganglia: direct NT-3 activation of TrkB neurons in vivo. Fariñas, I., Wilkinson, G.A., Backus, C., Reichardt, L.F., Patapoutian, A. Neuron (1998) [Pubmed]
  30. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 complement and cooperate with each other sequentially during visceral neuron development. ElShamy, W.M., Ernfors, P. J. Neurosci. (1997) [Pubmed]
  31. Support of trigeminal sensory neurons by nonneuronal p75 neurotrophin receptors. Fan, L., Girnius, S., Oakley, B. Brain Res. Dev. Brain Res. (2004) [Pubmed]
  32. Novel roles for neurotrophins are suggested by BDNF and NT-3 mRNA expression in developing neurons. Schecterson, L.C., Bothwell, M. Neuron (1992) [Pubmed]
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