Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021:2277:1-13.
doi: 10.1007/978-1-0716-1270-5_1.

Allotopic Expression of ATP6 in Mouse as a Transgenic Model of Mitochondrial Disease

David A Dunn  1 , Carl A Pinkert  2
Affiliations

Allotopic Expression of ATP6 in Mouse as a Transgenic Model of Mitochondrial Disease

David A Dunn et al. Methods Mol Biol. 2021.

Abstract

Progress in animal modeling of polymorphisms and mutations in mitochondrial DNA (mtDNA) is not as developed as nuclear transgenesis due to a host of cellular and physiological distinctions. mtDNA mutation modeling is of critical importance as mutations in the mitochondrial genome give rise to a variety of pathological conditions and play a contributing role in many others. Nuclear localization and transcription of mtDNA genes followed by cytoplasmic translation and transport into mitochondria (allotopic expression, AE) provide an opportunity to create in vivo modeling of a targeted mutation in mitochondrial genes. Accordingly, such technology has been suggested as a strategy for gene replacement therapy in patients harboring mitochondrial DNA mutations. Here, we use our AE approach to transgenic mouse modeling of the pathogenic human T8993G mutation in mtATP6 as a case study for designing AE animal models.

Keywords: ATP6; Allotopic expression; Animal modeling; Mitochondrial disease; Transgenic mouse; mtDNA.

PubMed Disclaimer

References

    1. Timmis JN, Ayliffe MA, Huang CY et al (2004) Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat Rev Genet 5:123–135 - PubMed
    1. Nagley P, Devenish RJ (1989) Leading organellar proteins along new pathways: the relocation of mitochondrial and chloroplast genes to the nucleus. Trends Biochem Sci 14:31–35
    1. Dunn DA, Cannon MV, Irwin MH et al (2012) Animal models of human mitochondrial DNA mutations. Biochim Biophys Acta 1820:601–607 - PubMed
    1. Wan X, Pei H, Zhao M et al (2016) Efficacy and safety of rAAV2-ND4 treatment for Leber’s hereditary optic neuropathy. Sci Rep 6:21587 - PubMed - PMC
    1. Guy J, Feuer WJ, Davis JL et al (2017) Gene therapy for Leber hereditary optic neuropathy: low- and medium-dose visual results. Ophthalmology 124:1621–1634 - PubMed

Publication types

Substances

LinkOut - more resources