Nerve regeneration in Wld(s) mice is normalized by actinomycin D

Brain Res. 2000 Jun 9;867(1-2):1-8. doi: 10.1016/s0006-8993(00)02140-5.


Injured nerves of Wld(s) mice neither degenerate nor regenerate for several weeks. We have conjectured that Wld(s) axons have the ability to regenerate but its expression is impaired by the Schwann cells of the undegenerated distal stump. To test this conjecture, transcription was locally arrested with actinomycin D (ActD), nerves were crushed, and regrowth was evaluated. In normal CD1 nerves injected with ActD 3 days before the crush, the rate of elongation was not affected but the delay of regrowth was shortened. In sharp contrast, ActD normalized the elongation of Wld(s) axons. When Wld(s) nerves were crushed past the treated segment, axons did not regenerate. After 7, but not 4, days of treatment, intact CD1 and Wld(s) axons presented a local sprouting response. We conclude that Wld(s) axons can regenerate in a normal way but do not do so because the undegenerated Schwann cells of the distal stump repress the regrowth program. We present a model axon that includes a destruction program and a post-transcriptional trophic regulation of its phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Axons / ultrastructure
  • Dactinomycin / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microscopy, Electron
  • Nerve Crush
  • Nerve Degeneration / physiopathology
  • Nerve Regeneration / drug effects*
  • Nucleic Acid Synthesis Inhibitors / pharmacology*
  • Schwann Cells / physiology
  • Schwann Cells / ultrastructure
  • Sciatic Nerve / cytology
  • Sciatic Nerve / physiology


  • Nucleic Acid Synthesis Inhibitors
  • Dactinomycin