Severe sensory and sympathetic deficits in mice lacking neurotrophin-3

Nature. 1994 Jun 23;369(6482):658-61. doi: 10.1038/369658a0.


During development, neurotrophins help shape the nervous system by regulating neuronal survival and differentiation. Neurotrophin-3 (refs 1-5) is the most abundant neurotrophin during early development. Neurons responsive to neurotrophin-3 in vitro include primary sensory, sympathetic, motor, enteric, locus coeruleus, hippocampal and cerebellar neurons (ref. 9 for example). Here we report that mice lacking neurotrophin-3 have severe deficits in sensory and sympathetic populations. These mice lack muscle spindles and show abnormal limb positions. In contrast, motor neurons, the enteric nervous system, and the major anatomical regions of the central nervous system seem to develop normally. Comparisons with mutants deficient in other neurotrophins or their receptors indicate that some neurons require more than one neurotrophin during embryogenesis and suggest that neurotrophin-3 functions by binding receptors in addition to its primary receptor trkC (ref. 16). In particular, neurotrophin-3 is essential for survival of sympathetic and sensory neurons that later become dependent on nerve growth factor or brain-derived neurotrophic factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Count
  • Mice
  • Muscles / pathology
  • Nerve Growth Factors / deficiency
  • Nerve Growth Factors / physiology*
  • Nervous System Diseases / etiology*
  • Nervous System Diseases / pathology
  • Neurons, Afferent* / metabolism
  • Neurotrophin 3
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, trkC
  • Receptors, Growth Factor / metabolism
  • Sympathetic Nervous System* / metabolism
  • Sympathetic Nervous System* / pathology


  • Nerve Growth Factors
  • Neurotrophin 3
  • Receptors, Growth Factor
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkC