Varying survival of motoneurons and activation of distinct molecular mechanism in response to altered peripheral myelin protein 22 gene dosage |
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Authors: | Heiner Nattkämper Hartmut Halfter Mohammad R Khazaei Tina Lohmann Burkhard Gess Martin Eisenacher†‡ Edith Willscher† Peter Young§ |
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Institution: | Department of Neurology, University Hospital of Münster, Münster, Germany; Functional Genomics Center, IZKF Münster, University of Münster, Münster, Germany; Department of Human Genetics, Ruhr-University of Bochum, Bochum, Germany; IZKF Münster, University of Münster, Münster, Germany |
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Abstract: | Alteration in the expression level of peripheral myelin protein 22 (PMP22) is the most frequent cause for demyelinating neuropathies of Charcot-Marie-Tooth type. Here, we demonstrate a loss of motoneurons (MNs) in the spinal cords from transgenic mice over-expressing Pmp22 ( Pmp22 tg ) while mice lacking Pmp22 Pmp22 ko ; knockout (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. Remarkably, the MNs of the Pmp22 ko and Pmp22 tg mice showed different expression profiles because of 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 Gap 43 and Sprr 11a. 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 ( Bex 1) and desmoplakin ( Dsp ) that had recently been found up-regulated in MNs of human amyotrophic lateral sclerosis patients. |
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Keywords: | axonal regeneration Charcot-Marie-Tooth demyelination microarray motoneurons neuropathy |
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