References
Query Results -- Details
MGI Accession ID: MGI:3835906
J Number: J:145737
Other Accession IDs:
Title: Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging neurons.
Authors: Fukui H; Moraes CT
Journal: Hum Mol Genet
Volume: 18
Issue: 6
Date: 2009 Mar 15
Year: 2009
Pages: 1028-36
Review Status: Peer Reviewed
Abstract:
Age-dependent accumulation of partially deleted mitochondrial DNA (DeltamtDNA) has been suggested to contribute to aging and the development of age-associated diseases including Parkinson's disease. However, the molecular mechanisms underlying the generation and accumulation of DeltamtDNA have not been addressed in vivo. In this study, we have developed a mouse model expressing an inducible mitochondria-targeted restriction endonuclease (PstI). Using this system, we could trigger mtDNA double-strand breaks (DSBs) in adult neurons. We found that this transient event leads to the generation of a family of DeltamtDNA with features that closely resemble naturally-occurring mtDNA deletions. The formation of these deleted species is likely to be mediated by yet uncharacterized DNA repairing machineries that participate in homologous recombination and non-homologous end-joining. Furthermore, we obtained in vivo evidence that DeltamtDNAs with larger deletions accumulate faster than those with smaller deletions, implying a replicative advantage of smaller mtDNAs. These findings identify DSB, DNA repair systems and replicative advantage as likely mechanisms underlying the generation and age-associated accumulation of DeltamtDNA in mammalian neurons.
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