Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/- mice.
ABSTRACT Charcot-Marie-Tooth neuropathies are frequent hereditary disorders of the nervous system and most cases remain without a molecular definition. Mutations in transcription factors have been previously associated to various types of this disease. Mice carrying a null mutation in Ebf2 transcription factor present peripheral nerve abnormalities. To get insight into Ebf2 function in peripheral nervous system, here we characterize the peripheral neuropathy affecting these mice. We first show that Ebf2 is largely expressed in peripheral nerve throughout postnatal development, its expression being not only restricted to non-myelin forming Schwann cells, but also involving myelin forming Schwann cells and the perineurium. As a consequence, the onset of myelination is delayed and Schwann cell differentiation markers are downregulated in Ebf2-/- mice. Later in development, myelin pathology appears less severe and characterized by isolated clusters of hypomyelinated fibers. However, we find defects in the nerve architecture, such as abnormalities of the nodal region and shorter internodal length. Furthermore, we demonstrate a significant decrease in axonal calibre, with a lack of large calibre axons, and a severe impairment of motor nerve conduction velocity and amplitude, whereas the sensory nerve parameters are less affected. Interestingly, a clinical case with peripheral motor neuropathy and clinical features similar to Ebf2-/- mice phenotype was associated with a deletion encompassing EBF2 human genomic locus. These findings demonstrate that Ebf2 is a new molecule implicated in peripheral nerve development and a potential candidate gene for peripheral nerve disorders.
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ABSTRACT: The motor nerve conduction velocity in rat tails was serially measured in vivo with controlled constant subcutaneous temperature.The conduction velocity increased linearly at a rate of about 1.3 m/sec per degree between 24°C and 42°C and increased during growth up to about 180 days. Conduction velocities before and after 96 h of starvation showed no significant changes in vitamin-administered rats, but did show significant changes in non-vitamin-administered rats. Conduction velocity in the alloxanized diabetic group decreased significantly in comparison to the value before the injection of alloxan and to that of the non-diabetic group.These results demonstrate that repetitive determinations of conduction velocity are possible in vivo with temperature control of rat tails and with minimal error in the measurement of nerve length.The method is simple, reliable for serial determinations of nerve conduction velocities in rats, and especially useful in experimental studies of peripheral nerve impairment whatever the cause.RésuméLa vitesse de conduction nerveuse motrice au niveau de la queue du rat a été mesurée de façon sérielle in vivo en même temps que la température sous-cutanée était en permanence controlée.La vitesse de conduction augmente de façon linéaire à une vitesse d'environ 1.3 m/sec par degré entre 24°C et 42°C et augmente au cours de la croissance jusqu'à environ 180 jours. La vitesse de conduction avant et après 96 h de privation de nourriture ne montre aucune modification significative chez les rats qui ont reçu des vitamines, mais montre des modifications significatives chez des rats qui n'ont pas reçu de vitamines. Dans le groupe d'animaux diabétiques à l'alloxane, la vitesse de conduction diminue de façon significative par comparaison à sa valeur avant l'injection d'alloxane et par comparaison à celle du groupe non diabétique.Ces résultats montrent que les mesures répétitives de la vitesse de conduction sont possibles in vivo avec contrôle de la température de la queue du rat et avec une erreur minime dans les mesures de la longueur nerveuse.Cette méthode est simple, permettant des mesures sérielles fiables des vitesses de conduction nerveuse chez le rat et particulièrement utile dans les études expérimentales des perturbations nerveuses périphériques quelle qu'en soit la cause.Electroencephalography and Clinical Neurophysiology 09/1973; 35(2):125-31.
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ABSTRACT: The thickness of the myelin sheath is known to increase with axon caliber, but there is also a superimposed, slight variation in sheath thickness depending on whether a fiber of a given caliber has very long or very short internodes. This relationship between myelin sheath thickness and the geometric proportion of the internode has been shown in subserial sections of isolated nerve fibers. It allows a prediction of sheath thickness from the quotient internode length/axon caliber, or conversely, a prediction of internode foreshortening from sheath thickness. We applied this new approach to the analysis of sciatic fiber populations of frogs, mice, rats and cats. The geometric proportions of these fibers were defined by the quotient internode length/fiber caliber. This quotient was compared with minor variation in sheath thickness as determined with a computer-assisted technique measuring large numbers of fibers in low-power electron micrographs. The method also calculated fiber shrinkage and recalculated all data for circular fiber profiles. The data obtained confirmed previous electron microscopic measurements showing that there is a slight reduction in sheath thickness when a fiber of a given caliber has relatively short internodes, and vice versa. A population of very thin, thinly myelinated fibers was also revealed. Sheath thickness and the geometric proportions of internodes in frogs differed markedly from those in mammals.Journal of Neuropathology and Experimental Neurology 02/1985; 44(1):60-72. · 4.35 Impact Factor
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ABSTRACT: The thickness of the myelin sheath of nerve fibers was traditionally assessed solely as a function of axon caliber. Studies concerning the additional effect of variation in internode length are of relatively recent date. Carefully calibrated measurements of sheath thickness and internode geometry were used in this study to define an equation to predict the approximate number of lamellae from axon caliber and internode length, for normal and regenerated peripheral nerve fibers, and for fibers from hypomyelinated murine mutants. The definition of sheath thickness thus obtained was compared with different assumptions on the biophysical nature of myelin sheath resistance. The observed relations between sheath thickness and internode geometry were not compatible with an effective adjustment of sheath thickness to a radial flow of current across the sheath. Conversely, sheath thickness was found to vary in such a way that the resistance of the spiral path between the lamellae was matched precisely to axonal current density. The calculated resistance of the spiral leakage path, furthermore, was equal to measured sheath resistance. This new concept reconciles low sheath resistance with a high resistance of the myelin leaflet, yielding, at the same time, a fine tuning of sheath resistance to variations of internode geometry.Experimental Neurology 05/1986; 92(1):234-47. · 4.65 Impact Factor