Related Experiment Video
Updated: May 29, 2026
A Repetitive Concussive Head Injury Model in Mice
Published on: October 12, 2016
Trauma does not accelerate neuronal degeneration in Fig4 insufficient mice
Qing Yan1, Jiasong Guo, Xuebao Zhang
1Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Abstract:
Fig4 null reduces phosphatidylinositol-3,5-diphosphate concentration and causes severe neuronal degeneration in both pale-tremor (plt) mice and patients with Charcot-Marie-Tooth disease type 4J (CMT4J), an inherited condition with recessive mutations in FIG4. Our previous study shows that minor trauma is associated with an accelerated course of motor neuron degeneration in patients with CMT4J. Heterozygous loss of FIG4 function has been suggested to be a risk factor in developing sporadic amyotrophic lateral sclerosis. We therefore hypothesize that minor trauma may trigger or exacerbate motor neuron degeneration in mice with fig4 haploinsufficiency (plt+/-). We have studied 18 wild-type and 18 plt+/- mice and created nerve injury by compressing the sciatic nerve. Outcomes in the mice were evaluated by nerve conduction study, Rotarod, and nerve morphology. No differences were found between wild-type and plt+/- mice. Taken together, our results demonstrate that haploinsufficiency of fig4 does not impose risks in rodents to develop neuronal degeneration in either naïve or traumatic conditions.
Insights
Fig4 haploinsufficiency does not increase neuronal degeneration risk in mice, even after sciatic nerve injury. This study found no evidence that reduced FIG4 function exacerbates motor neuron damage under trauma conditions.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- FIG4 mutations cause neuronal degeneration in pale-tremor (plt) mice and Charcot-Marie-Tooth disease type 4J (CMT4J).
- Minor trauma accelerates motor neuron degeneration in CMT4J patients.
- Heterozygous FIG4 loss is a potential risk factor for sporadic amyotrophic lateral sclerosis.
Purpose of the Study:
- To investigate if minor trauma triggers or worsens motor neuron degeneration in mice with fig4 haploinsufficiency (plt+/-).
Main Methods:
- Studied 18 wild-type and 18 plt+/- mice.
- Induced nerve injury by sciatic nerve compression.
- Evaluated outcomes using nerve conduction studies, Rotarod tests, and nerve morphology.
Main Results:
- No significant differences were observed between wild-type and plt+/- mice in any tested condition.
- Sciatic nerve injury did not lead to increased neuronal degeneration in fig4 haploinsufficient mice.
Conclusions:
- Haploinsufficiency of FIG4 does not confer increased risk for neuronal degeneration in rodents, neither in normal conditions nor following traumatic injury.
