title: Trauma does not accelerate neuronal degeneration in Fig4 insufficient mice.
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.
authors.affiliation: Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yan
authors.forename: Jiasong
authors.initials: J
authors.lastname: Guo
authors.forename: Xuebao
authors.initials: X
authors.lastname: Zhang
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Bai
authors.forename: Lily
authors.initials: L
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D005260:Female; D005420:Flavoproteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D057895:Haploinsufficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D009410:Nerve Degeneration / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D009431:Neural Conduction / Q000235:genetics; D000072180:Phosphoinositide Phosphatases; D012307:Risk Factors; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology*; D020426:Sciatic Neuropathy / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D005420:Flavoproteins; C522216:Fig4 protein, mouse; D000072180:Phosphoinositide Phosphatases