Center forBiomedical Network Research on Rare Diseases

Valencia, Spain

Center forBiomedical Network Research on Rare Diseases

Valencia, Spain
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Del Amo V.L.,Program of Rareand Genetic Diseases | Del Amo V.L.,Center forBiomedical Network Research on Rare Diseases | Seco-Cervera M.,Center forBiomedical Network Research on Rare Diseases | Seco-Cervera M.,University of Valencia | And 7 more authors.
Human Molecular Genetics | Year: 2015

One of the genes involved in Charcot-Marie-Tooth (CMT) disease, an inherited peripheral neuropathy, is GDAP1. In this work, we show that there is a true ortholog of this gene in Drosophila, which we have named Gdap1. By up- and down-regulation of Gdap1 in a tissue-specific manner, we show that altering its levels of expression produces changes in mitochondrial size, morphology and distribution, and neuronal and muscular degeneration. Interestingly, muscular degeneration is tissue-autonomous and not dependent on innervation. Metabolic analyses of our experimental genotypes suggest that alterations in oxidative stress are not a primary cause of the neuromuscular degeneration but a long-term consequence of the underlying mitochondrial dysfunction. Our results contribute to a better understanding of the role of mitochondria in CMT disease and pave the way to generate clinically relevant disease models to study the relationship between mitochondrial dynamics and peripheral neurodegeneration. © The Author 2014. Published by Oxford University Press. All rights reserved.

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