Neurological phenotype and reduced lifespan in heterozygous Tim23 knockout mice, the first mouse model of defective mitochondrial import

Uwe Ahting, Thomas Floss, Nikolas Uez, Ilka Schneider-Lohmar, Lore Becker, Eva Kling, Arcangela Iuso, Andreas Bender, Martin Hrabé de Angelis, Valérie Gailus-Durner, Helmut Fuchs, Thomas Meitinger, Wolfgang Wurst, Holger Prokisch, Thomas Klopstock

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The Tim23 protein is the key component of the mitochondrial import machinery. It locates to the inner mitochondrial membrane and its own import is dependent on the DDP1/TIM13 complex. Mutations in human DDP1 cause the Mohr-Tranebjaerg syndrome (MTS/DFN-1; OMIM #304700), which is one of the two known human diseases of the mitochondrial protein import machinery. We created a Tim23 knockout mouse from a gene trap embryonic stem cell clone. Homozygous Tim23 mice were not viable. Heterozygous F1 mutants showed a 50% reduction of Tim23 protein in Western blot, a neurological phenotype and a markedly reduced life span. Haploinsufficiency of the Tim23 mutation underlines the critical role of the mitochondrial import machinery for maintaining mitochondrial function.

Original languageEnglish
Pages (from-to)371-376
Number of pages6
JournalBBA - Bioenergetics
Volume1787
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

Keywords

  • DDP1
  • Mitochondrial import machinery
  • Tim23 knockout mouse

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