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Mitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice

Nature Genetics volume 18, pages 231–236 (1998)Cite this article

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.

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Authors and Affiliations

  1. Department of Molecular Medicine, Center for Molecular Medicine 18:02, Karolinska Hospital, S-17176, Stockholm, Sweden

    Nils-Göran Larsson, Jianming Wang & Hans Wilhelmsson

  2. Department of Woman and Child Health, Karolinska Hospital, S-17176, Stockholm, Sweden

    Hans Wilhelmsson

  3. Department of Pathology, Sahlgrenska Hospital, S-41345, Göteborg, Sweden

    Anders Oldfors

  4. INSERM U393, Hdpital des Enfants-Malades, Paris, 75015, France

    Pierre Rustin

  5. Department of Anatomy, UCSF School of Medicine, San Francisco, California, 94143, USA

    Mark Lewandoski

  6. Departments of Pediatrics and Genetics, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, 94305-5428, USA

    Gregory S. Barsh

  7. Howard Hughes Medical Institute, 4000 Jones Bridge Rd, Chevy Chase, Maryland, 20815-6789, USA

    David A. Clayton

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  1. Nils-Göran Larsson
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Larsson, NG., Wang, J., Wilhelmsson, H. et al. Mitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice. Nat Genet 18, 231–236 (1998). https://doi.org/10.1038/ng0398-231

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