Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/

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Neurobiol Dis. 2011 Jan

Both Schwann cell and axonal defects cause motor peripheral neuropathy in

Ebf2-/- mice.

Giacomini C, La Padula V, Schenone A, Leandri M, Contestabile A, Moruzzo D,

Goutebroze L, Consalez GG, Benfenati F, Corradi A.

Department of Experimental Medicine, Section of Human Physiology, University of

Genova, Italy.

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.