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TitleDifferential mtDNA damage patterns in a transgenic mouse model of Machado-Joseph disease (MJD/SCA3)
Author(s)Ramos, Amanda
Kazachkova, Nadiya
Silva, Francisca
Maciel, P.
Fernandes, Anabela Silva
Silva, Sara Carina Duarte
Santos, Cristina
Lima, Manuela
KeywordsMitochondrial DNA
mtDNA damage
Machado-Joseph disease
Transgenic mouse model
Neurodegenerative disorder
Polyglutamine disorder
Issue date2015
JournalJournal of Molecular Neuroscience
CitationRamos, A., Kazachkova, N., Silva, F., Maciel, P., Silva-Fernandes, A., Duarte-Silva, S., . . . Lima, M. (2015). Differential mtDNA Damage Patterns in a Transgenic Mouse Model of Machado-Joseph Disease (MJD/SCA3). Journal of Molecular Neuroscience, 55(2), 449-453. doi: 10.1007/s12031-014-0360-1
Abstract(s)Mitochondrial dysfunction has been associated with late onset neurodegenerative disorders, among which is Machado-Joseph disease (MJD/SCA3). In a previous study, using a transgenic mouse model of MJD, we reported a decrease in mitochondrial DNA (mtDNA) copy number and an accumulation of the 3876-bp deletion with age and with phenotype development. We extended this study by analyzing the pattern of mtDNA depletion and the accumulation of the 3876-bp deletion in 12 older transgenic (TG) and 4 wild-type (wt) animals, and by investigating the accumulation of somatic mutations in the D-loop region in 76 mice (42 TG and 34 wt). mtDNA damage was studied in TG and wt mice at different ages and tissues (blood, pontine nuclei, and hippocampus). Results for older mice demonstrate an accumulation of the mtDNA 3867-bp deletion with age, which was more pronounced in TG animals. Furthermore, the tendency for mtDNA copy number decrease with age, in all analyzed tissues of TG and wt animals, was also confirmed. No point mutations were detected in the D-loop, neither in TG nor wt animals, in any of the tissues analyzed. Due to the absence of mtDNA somatic mutations, we can suggest that mtDNA point mutation accumulation cannot be used to monitor the development and progression of the phenotype in this mouse model and likely in any MJD mice model. The present results further confirm not only the association between mtDNA alterations (copy number and deletions) and age, but also between such alterations and the expression of the mutant ataxin-3 in TG mice.
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AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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