Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice - PubMed (original) (raw)
Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice
N G Larsson et al. Nat Genet. 1998 Mar.
Abstract
The regulation of mitochondrial DNA (mtDNA) expression is crucial for mitochondrial biogenesis during development and differentiation. We have disrupted the mouse gene for mitochondrial transcription factor A (Tfam; formerly known as m-mtTFA) by gene targetting of loxP-sites followed by cre-mediated excision in vivo. Heterozygous knockout mice exhibit reduced mtDNA copy number and respiratory chain deficiency in heart. Homozygous knockout embryos exhibit a severe mtDNA depletion with abolished oxidative phosphorylation. Mutant embryos proceed through implantation and gastrulation, but die prior to embryonic day (E)10.5. Thus, Tfam is the first mammalian protein demonstrated to regulate mtDNA copy number in vivo and is essential for mitochondrial biogenesis and embryonic development.
Comment in
- An essential guide to mtDNA maintenance.
Turnbull DM, Lightowlers RN. Turnbull DM, et al. Nat Genet. 1998 Mar;18(3):199-200. doi: 10.1038/ng0398-199. Nat Genet. 1998. PMID: 9500531 No abstract available.
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