Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease

Cell. 1993 Apr 9;73(1):23-33. doi: 10.1016/0092-8674(93)90157-l.


Excessive accumulation of neurofilaments in the cell bodies and proximal axons of motor neurons is a major pathological hallmark during the early stages of many human motor neuron diseases. To test directly the consequence of overexpression of the major neurofilament subunit NF-L, we produced transgenic mice that accumulate NF-L to approximately 4-fold the normal level in the sciatic nerve. In young animals, the motor neurons of the ventral horn of the spinal cord have massive accumulations of neurofilaments, swollen perikarya, and eccentrically localized nuclei. NF-L accumulation is accompanied by an increased frequency of axonal degeneration, proximal axon swelling, and severe skeletal muscle atrophy. These data indicate that extensive accumulation of neurofilaments in motor neurons can trigger the neurodegenerative process.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / pathology
  • Mice
  • Mice, Transgenic
  • Motor Neuron Disease / metabolism
  • Motor Neuron Disease / pathology*
  • Motor Neurons / pathology
  • Muscular Atrophy / metabolism
  • Nerve Degeneration
  • Neurofilament Proteins / biosynthesis*
  • Neurofilament Proteins / metabolism
  • Phosphorylation
  • Spinal Cord / pathology


  • Neurofilament Proteins
  • neurofilament protein L
  • neurofilament protein H