Staunton, Lisa and Jockusch, Harald and Wiegand, Christiane and Albrecht, Timo and Ohlendieck, Kay (2011) Identification of secondary effects of hyperexcitability by proteomic profiling of myotonic mouse muscle. Molecular BioSystems, 8. pp. 2480-2489. ISSN 1742-206X

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Abstract

Myotonia is a symptom of various genetic and acquired skeletal muscular disorders and is characterized by hyperexcitability of the sarcolemma. Here, we have performed a comparative proteomic study of the genetic mouse models ADR, MTO and MTO*5J of human congenital myotonia in order to determine myotonia-specific changes in the global protein complement of gastrocnemius muscle. Proteomic analyses of myotonia in the mouse, which is caused by mutations in the gene encoding the muscular chloride channel Clc1, revealed a generally perturbed protein expression pattern in severely affected ADR and MTO muscle, but less pronounced alterations in mildly diseased MTO*5J mice. Alterations were found in major metabolic pathways, the contractile machinery, ion handling elements, the cellular stress response and cell signaling mechanisms, clearly confirming a glycolytic-to-oxidative transformation process in myotonic fast muscle. In the long-term, a detailed biomarker signature of myotonia will improve our understanding of the pathobiochemical processes underlying this disorder and be helpful in determining how a single mutation in a tissue-specific gene can trigger severe downstream effects on the expression levels of a very large number of genes in contractile tissues.

Item Type:	Article
Keywords:	hyperexcitability; proteomic profiling; myotonic mouse muscle; Myotonia; skeletal muscular disorders;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	7488
Identification Number:	https://doi.org/10.1039/C1MB05043E
Depositing User:	Prof. Kay Ohlendieck
Date Deposited:	07 Oct 2016 10:43
Journal or Publication Title:	Molecular BioSystems
Publisher:	Royal Society of Chemistry
Refereed:	Yes
Funders:	Health Research Board (HRB), Fonds der Chemischen Industrie (FCI)
URI:	http://pubs.rsc.org
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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