title: Sensorimotor and cognitive function of a NEFL(P22S) mutant model of Charcot-Marie-Tooth disease type 2E.
abstract: Charcot-Marie-Tooth (CMT) disease is the most frequently encountered hereditary disease causing sensorimotor neuropathies and slowly progressive muscle weakness and atrophy. The P22S mutation of the NEFL gene encoding the light polypeptide neurofilament (NFL) is associated with CMT. To understand more clearly the pathogenesis of sensorimotor dysfunction in CMT, we generated transgenic mice with the NEFL(P22S) mutation under the tet-off tetracycline regulated system with involvement of the Thy1 neuron-specific promoter. NEFL(P22S) transgenic mice exhibited extended duration of the hindlimb clasping response and gait anomalies, as well as sensorimotor deficits in stationary beam and suspended bar tests. In addition, the NEFL(P22S) mice were deficient in the reversal phase of left-right discrimination learning in a water maze. This model mimics some aspects of human CMT pathology and provides an opportunity of ameliorating CMT symptoms with experimental therapies.
authors.affiliation: CHUL Research Center and Department of Molecular Medicine, Laval University, 2705 Laurier boul., Québec G1V 4G2, Canada. Mohammed.Filali@crchul.ulaval.ca
authors.forename: Mohammed
authors.initials: M
authors.lastname: Filali
authors.forename: Florence
authors.initials: F
authors.lastname: Dequen
authors.forename: Robert
authors.initials: R
authors.lastname: Lalonde
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Julien
mesh_terms: D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000523:psychology; D003071:Cognition / Q000502:physiology*; D004193:Discrimination Learning / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D005684:Gait / Q000502:physiology; D006614:Hindlimb / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D016900:Neurofilament Proteins / Q000235:genetics*; D058748:Pain Perception / Q000502:physiology; D010812:Physical Stimulation; D004856:Postural Balance / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D012193:Reversal Learning / Q000502:physiology; D012684:Sensory Thresholds / Q000502:physiology; D013028:Space Perception / Q000502:physiology
chemical_list: D016900:Neurofilament Proteins; C044882:neurofilament protein L