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Updated: Jul 4, 2026

In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration
06:35

In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration

Published on: June 15, 2018

Mutation of FIG4 causes a rapidly progressive, asymmetric neuronal degeneration

Xuebao Zhang1, Clement Y Chow, Zarife Sahenk

  • 1Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Brain : a Journal of Neurology
|June 17, 2008
PubMed

Insights

Charcot-Marie-Tooth disease type-4J (CMT4J), caused by FIG4 gene mutations, presents as motor neuron disease with progressive paralysis. Vacuoles obstruct organelle trafficking, potentially causing neurodegeneration.

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Recessive Charcot-Marie-Tooth disease type-4J (CMT4J) and its pale tremor (plt) mouse model result from mutations in the FIG4 gene.
  • The FIG4 gene encodes a PI(3,5)P(2) 5-phosphatase crucial for cellular processes.

Observation:

  • The 9-year clinical course of two CMT4J siblings revealed asymmetric, rapidly progressive paralysis with absent sensory symptoms.
  • Fibroblast imaging showed impaired intracellular organelle trafficking due to vacuole obstruction in CMT4J patients.
  • Characterization of plt mice revealed axonal degeneration in motor and sensory neurons.

Findings:

  • CMT4J clinically mimics motor neuron disease despite sensory axon reduction.
  • Vacuoles physically obstruct organelle trafficking, a novel mechanism in neurodegeneration.
  • plt mice exhibited limited demyelination and no TUNEL staining or ubiquitinated protein accumulation.

Implications:

  • This study provides the first natural history documentation of CMT4J.
  • Physical obstruction of organelle trafficking by vacuoles represents a potential novel cellular mechanism driving neurodegeneration.
  • Understanding this mechanism may offer new therapeutic targets for CMT4J and related neurodegenerative disorders.

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