Manipulation of mitochondrial DNA gene expression in the mouse

José P. Silva, Nils Göran Larsson

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Mitochondrial dysfunction due to impaired respiratory chain function is increasingly recognized as an important cause of human disease. Mitochondrial disorders are relatively common and have an estimated incidence of 1:10,000 live births. There are more than 100 different point mutations and numerous large rearrangements of mitochondrial DNA (mtDNA; mainly single deletions) that cause human disease. We aimed at obtaining an animal model to study physiological aspects of mtDNA mutation disorders. There are as yet unsolved technical problems associated with transfection of mammalian mitochondria. We therefore choose to manipulate mtDNA expression by targeting of the nuclear gene encoding Tfam. We utilised the cre-loxP recombination system to disrupt Tfam since this system allows manipulation of respiratory chain function in selected mouse tissues. We have found increased cell death or apoptosis induction in both germ line and tissue-specific Tfam knockouts. Our results further suggest that increased production of reactive oxygen species (ROS) is not a prominent feature in cells with impaired mtDNA expression.

Original languageEnglish (US)
Pages (from-to)106-110
Number of pages5
JournalBiochimica et Biophysica Acta - Bioenergetics
Issue number1-3
StatePublished - Sep 10 2002


  • Aging
  • Apoptosis
  • cre-loxP
  • Mouse model
  • mtDNA mutation
  • ROS

ASJC Scopus subject areas

  • Biophysics


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