Dokument: The α-chemokine CXCL14 is up-regulated in the sciatic nerve of a mouse model of Charcot-Marie-Tooth disease type 1A and alters myelin gene expression in Schwann cells

Titel:The α-chemokine CXCL14 is up-regulated in the sciatic nerve of a mouse model of Charcot-Marie-Tooth disease type 1A and alters myelin gene expression in Schwann cells
URL für Lesezeichen:https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=10131
URN (NBN):urn:nbn:de:hbz:061-20090115-105618-7
Kollektion:Dissertationen
Sprache:Englisch
Dokumententyp:Wissenschaftliche Abschlussarbeiten » Dissertation
Medientyp:Text
Autor: Barbaria, Elena Maria [Autor]
Dateien:
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Dateien vom 14.01.2009 / geändert 14.01.2009
Beitragende:Prof. Dr. Müller, Hans Werner [Gutachter]
Prof. Dr. Mehlhorn, Heinz [Gutachter]
Dewey Dezimal-Klassifikation:500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie
Beschreibung:Charcot-Marie-Tooth (CMT) disease is the most common human hereditary peripheral neuropathy, affecting approximately 1 in 2500 individuals. It is clinically characterised by progressive weakness and atrophy of the distal limb muscles. CMT type 1A (CMT1A), transmitted as an autosomal dominant trait, affects approximately 50% of all CMT patients. This disorder is mostly caused by a 1.5-Mb tandem duplication of chromosome 17, comprising the gene for the peripheral myelin protein 22-kDa (PMP22). Although there are numerous studies on the functional role of PMP22, the mechanisms of myelin degeneration under conditions of PMP22 overexpression are not entirely clear. Most of the transgenic animal models that were previously generated express multiple copies of PMP22 and are characterised by dysmyelination, a feature seen in patients with Dejerine-Sottas syndrome (DSS). As models for CMT1A, both a transgenic rat mutant and the mouse mutant C61 showed mild PMP22 overexpression and slow progression of the disorder. Furthermore, histopathological features, such as de- and remyelination, hypermyelination and onion bulb formation, observed in the C61 mice, are similar to those seen in CMT1A patients. In order to investigate the mechanisms underlying PMP22 overexpression-related demyelination in a model comparable to human CMT1A, the transgenic mouse line C61 was chosen for this study. These mice carry four copies of the human yeast artificial chromosome (YAC) clone 49G7 encompassing the entire human PMP22 gene. In this thesis, analyses performed in the sciatic nerve of P7 C61 mice reveal up-regulation of myelin genes, as well as hypermyelination. Hypermyelinated fibres were previously described in CMT1A-patients, in the Pmp22-overexpressing rat as well as in adult PMP22-transgenic C61 mice, but they were never described before in a CMT1A model, at such young age. Hence, this study focuses on the early postnatal development of the peripheral nerves to unveil any gene expression alteration that might have an impact on the early pathogenesis of CMT1A.
Fachbereich / Einrichtung:Mathematisch- Naturwissenschaftliche Fakultät
Dokument erstellt am:15.01.2009
Dateien geändert am:14.01.2009
Promotionsantrag am:16.10.2008
Datum der Promotion:26.11.2008
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