Sensorimotor and cognitive function of a NEFL(P22S) mutant model of Charcot-Marie-Tooth disease type 2E.

Publication Type:

Journal Article

Authors:

Filali, Mohammed; Dequen, Florence; Lalonde, Robert; J-P Julien

Source:

Behav Brain Res, Volume 219, Issue 2, p.175-80 (2011)

Keywords:

Animals, Charcot-Marie-Tooth Disease, Cognition, Discrimination Learning, Functional Laterality, Gait, Hindlimb, Maze Learning, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Neurofilament Proteins, Pain Perception, Physical Stimulation, Postural Balance, Reflex, Reversal Learning, Sensory Thresholds, Space Perception

Abstract:

<p>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.</p>