IGF-I deficient mice show reduced peripheral nerve conduction velocities and decreased axonal diameters and respond to exogenous IGF-I treatment

J Neurobiol. 1999 Apr;39(1):142-52. doi: 10.1002/(sici)1097-4695(199904)39:1<142::aid-neu11>3.0.co;2-h.


Although insulin-like growth factor-I (IGF-I) can act as a neurotrophic factor for peripheral neurons in vitro and in vivo following injury, the role IGF-I plays during normal development and functioning of the peripheral nervous system is unclear. Here, we report that transgenic mice with reduced levels (two genotypes: heterozygous Igf1+/- or homozygous insertional mutant Igf1m/m) or totally lacking IGF-I (homozygous Igf1-/-) show a decrease in motor and sensory nerve conduction velocities in vivo. In addition, A-fiber responses in isolated peroneal nerves from Igf1+/- and Igf1-/- mice are impaired. The nerve function impairment is most profound in Igf1-/- mice. Histopathology of the peroneal nerves in Igf1-/- mice demonstrates a shift to smaller axonal diameters but maintains the same total number of myelinated fibers as Igf1+/+ mice. Comparisons of myelin thickness with axonal diameter indicate that there is no significant reduction in peripheral nerve myelination in IGF-I-deficient mice. In addition, in Igf1m/m mice with very low serum levels of IGF-I, replacement therapy with exogenous recombinant hIGF-I restores both motor and sensory nerve conduction velocities. These findings demonstrate not only that IGF-I serves an important role in the growth and development of the peripheral nervous system, but also that systemic IGF-I treatment can enhance nerve function in IGF-I-deficient adult mice.

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / physiology*
  • Axons / ultrastructure
  • Homozygote
  • In Vitro Techniques
  • Insulin-Like Growth Factor I / deficiency
  • Insulin-Like Growth Factor I / pharmacology*
  • Insulin-Like Growth Factor I / physiology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mutagenesis, Insertional
  • Nerve Fibers / physiology
  • Neural Conduction / drug effects
  • Neural Conduction / physiology*
  • Peroneal Nerve / drug effects
  • Peroneal Nerve / pathology
  • Peroneal Nerve / physiology*


  • Insulin-Like Growth Factor I