Peripheral myelin maintenance is a dynamic process requiring constant Krox20 exp

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J Neurosci. 2006 Sep 20;26(38):9771-9.

Peripheral myelin maintenance is a dynamic process requiring constant

Krox20 expression.

Decker L, Desmarquet-Trin-Dinh C, Taillebourg E, Ghislain J, Vallat

JM, Charnay P.

Institut National de la Sante et de la Recherche Medicale, U784,

Ecole Normale Superieure, 75230 Paris Cedex 05, France.

Onset of myelination in Schwann cells is governed by several

transcription factors, including Krox20/Egr2, and mutations affecting

Krox20 result in various human hereditary peripheral neuropathies,

including congenital hypomyelinating neuropathy (CHN) and Charcot-

Marie-Tooth disease (CMT). Similar molecular information is not

available on the process of myelin maintenance.

We have generated conditional Krox20 mutations in the mouse that

allowed us to develop models for CHN and CMT. In the latter case,

specific inactivation of Krox20 in adult Schwann cells results in

severe demyelination, involving rapid Schwann cell dedifferentiation

and increased proliferation, followed by an attempt to remyelinate

and a block at the promyelinating stage. These data establish that

Krox20 is not only required for the onset of myelination but that it

is also crucial for the maintenance of the myelinating state.

Furthermore, myelin maintenance appears as a very dynamic process in

which Krox20 may constitute a molecular switch between Schwann cell

myelination and demyelination programs.