Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice.

ABSTRACT: In humans, MPV17 mutations are responsible for severe mitochondrial depletion syndrome, mainly affecting the liver and the nervous system. To gain insight into physiopathology of MPV17-related disease, we investigated an available Mpv17 knockout animal model. We found severe mtDNA depletion in liver and, albeit to a lesser extent, in skeletal muscle, whereas hardly any depletion was detected in brain and kidney, up to 1 year after birth. Mouse embryonic fibroblasts did show mtDNA depletion, but only after several culturing passages, or in a serumless culturing medium. In spite of severe mtDNA depletion, only moderate decrease in respiratory chain enzymatic activities, and mild cytoarchitectural alterations, were observed in the Mpv17(-/-) livers, but neither cirrhosis nor failure ever occu

SUBMITTER: Viscomi C 

PROVIDER: S-EPMC2644642 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature