1A motor impairments research - from France

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Abstract from Neuroscience 2003;116(3):695-703

Close relationship between motor impairments and loss of functional

motoneurons in a Charcot-Marie-Tooth type 1A model.

Norreel JC, Vinay L, Fontes M, Clarac F.

Developpement et Pathologie du mouvement, CNRS, 31 Chemin J. Aiguier,

13402 20, Marseille Cedex, France

Charcot-Marie-Tooth disease type 1A is the most frequent hereditary

neuropathy affecting the peripheral nervous system. A partial

duplication of chromosome 17 (17p11.2) involving the PMP22 gene is

responsible for dysmyelination-demyelination processes leading to motor

and sensory impairments.Murine models of this disease are now widely

used to investigate the mechanisms occurring at the behavioural and

physiological levels. In this study, adult transgenic mice (6 months

old) having integrated 7 copies of the human PMP22 gene were used to

compare the motor performance, evaluated by using a complex locomotor

test (the rotarod test), with both the number of functional motoneurons

innervating the soleus muscle and the level of myelination in the

sciatic nerve. Two levels of motor deficits were detected and led us to

divide the population into two subgroups.In both impaired groups, the

level of

motor deficit was strongly correlated with the number of functional

motoneurons

evaluated by retrograde labeling from the muscle, but not with the

number of myelinated fibers or the thickness of the myelin sheath

(g-ratio). It therefore appears that the number of motor units may be a

key element in motor impairments observed in Charcot-Marie-Tooth disease

type 1A disease. These findings may have implications for therapeutic

procedures, which should focus on the survival of the motoneuronal pool

and/or the maintenance of functional neuro-muscular connexions to

reduce motor impairments in humans.