Varying Survival of Motoneurons and Activation of Distinct Molecular Mechanism i

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J Neurochem. 2009 May 31.

Varying Survival of Motoneurons and Activation of Distinct Molecular Mechanism

in Response to Altered peripheral myelin protein 22 Gene Dosage.

Nattkämper H, Halfter H, Khazaei MR, Lohmann T, Gess B, Eisenacher M, Willscher

E, Young P.

Department of Neurology, University Hospital of Münster, Albert-Schweitzer-Str.

33, D- 48129 Münster.

Alteration in the expression level of peripheral myelin protein 22 (PMP22) is

the most frequent cause for demyelinating neuropathies of Charcot-Marie-Tooth

(CMT) type.

Here, we demonstrate a loss of motoneurons (MNs) in the spinal cords from

transgenic mice overexpressing Pmp22 (Pmp22(tg)) while mice lacking Pmp22

(Pmp22(ko)) exhibited normal MN numbers at the symptomatic age of 60 days. In

order to describe the molecular changes in affected MNs, these cells were

isolated from lumbar spinal cords by laser-capture microdissection (LMD).

Remarkably, the MNs of the Pmp22(ko) - and Pmp22(tg) mice showed different

expression profiles due to the altered Pmp22 expression. The changes in the

expression profile of MNs from Pmp22(ko) mice resemble those described in MNs

from mice after nerve injury and included genes that had been described in

neuronal growth and regeneration like Gap43 and Sprr11a.

The changes detected in the expression pattern of MNs from Pmp22(tg) mice

exhibited fewer similarities to other expression patterns. The specific

expression pattern in the MNs of the Pmp22(ko) mice might contribute to the

better survival of the MNs.

Our study also revealed induction of genes like brain-expressed X-linked 1

(Bex1) and desmoplakin (Dsp) that had recently been found upregulated in MNs of

human ALS patients.