title: Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury.
abstract: Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L(E397K), which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L(E397K) mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K). Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L(E397K) mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K) mice provide a model for determining the efficacy of novel therapies.
authors.affiliation: Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA; Bond Life Sciences Center, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Villalón
authors.affiliation: Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA; Bond Life Sciences Center, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Dale
authors.affiliation: Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA; Bond Life Sciences Center, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Jones
authors.affiliation: CurRenji-Medx Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Hailian
authors.initials: H
authors.lastname: Shen
authors.affiliation: Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA; Bond Life Sciences Center, University of Missouri-Columbia, Columbia, MO 65211, USA. Electronic address: GarciaML@missouri.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Garcia
mesh_terms: D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D005121:Extremities / Q000503:physiopathology; D007839:Functional Laterality / Q000235:genetics; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D006801:Humans; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology; D008124:Locomotion / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D016900:Neurofilament Proteins / Q000235:genetics; D010641:Phenotype; D011597:Psychomotor Performance / Q000502:physiology; D020127:Recovery of Function / Q000235:genetics; D012585:Sciatica / Q000150:complications / Q000209:etiology / Q000235:genetics
chemical_list: D016900:Neurofilament Proteins; C044882:neurofilament protein L
keywords: Charcot–Marie–Tooth type 2E; Functional recovery; Gait alterations; Nerve injury; Neurofilament; Neuropathy exacerbation