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.
Copyright © 2011 Elsevier B.V. All rights reserved.