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Nerve conduction studies in the Twitcher mouse (murine globoid cell leukodystrophy).
Journal of the Neurological Sciences
|July 1, 1986
Summary
Globoid cell leukodystrophy in Twitcher mice shows early nerve conduction slowing and block, even before motor signs appear. Hematopoietic cell transplantation (HCT) did not restore nerve conduction velocity but preserved motor function.
Area of Science:
- Neuroscience
- Animal Models
- Biochemistry
Background:
- Globoid cell leukodystrophy (GCL) is a severe inherited lysosomal storage disorder.
- The Twitcher mouse (twi-C57BL/6J) serves as a valuable animal model for studying GCL pathogenesis.
- Understanding neuropathy progression is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To assess the progression of neuropathy in Twitcher mice using serial motor nerve conduction studies.
- To evaluate the impact of hematopoietic cell transplantation (HCT) on nerve conduction and motor function in this model.
- To elucidate the electrophysiological characteristics of nerve dysfunction in GCL.
Main Methods:
- Serial motor nerve conduction studies were performed on Twitcher mice and unaffected siblings from near birth to near death.
- Tibial nerve stimulation and plantar foot muscle recordings were used to measure motor conduction velocity (MCV), distal latency, and compound muscle action potentials (CMAPs).
- Parameters including CMAP amplitude and phase ratios (proximal vs. distal) were analyzed to assess nerve conduction block and uniformity.
Main Results:
- Twitcher mice exhibited significantly reduced MCV and altered CMAP ratios (pCMAP/dCMAP amplitude and phases) even before overt motor signs.
- As the disease progressed, MCV slowed further, and CMAP amplitudes decreased, suggesting diffuse, non-uniform slowing and proximal nerve block.
- Following HCT, MCV remained significantly reduced compared to controls, but motor function was preserved.
Conclusions:
- Early, non-uniform slowing and proximal nerve conduction block are key electrophysiological features of neuropathy in the Twitcher mouse model of GCL.
- Hematopoietic cell transplantation shows potential in preserving motor function despite persistent electrophysiological deficits.
- These findings highlight the complex pathophysiology of GCL neuropathy and the therapeutic potential of HCT.