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Lookup NU author(s): Holly Baines,
Dr Craig Stamp,
Dr Laura Greaves,
Dr Jim StewartORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Mutations of mtDNA are an important cause of human disease, but few animal models exist. Because mammalian mitochondria cannot be transfected, the development of mice with pathogenic mtDNA mutations has been challenging, and the main strategy has therefore been to introduce mutations found in cell lines into mouse embryos. Here, we describe a phenotype-driven strategy that is based on detecting clonal expansion of pathogenic mtDNA mutations in colonic crypts of founder mice derived from heterozygous mtDNA mutator mice. As proof of concept, we report the generation of a mouse line transmitting a heteroplasmic pathogenic mutation in the alanine tRNA gene of mtDNA displaying typical characteristics of classic mitochondrial disease. In summary, we describe a straightforward and technically simple strategy based on mouse breeding and histology to generate animal models of mtDNA-mutation disease, which will be of great importance for studies of disease pathophysiology and preclinical treatment trials.
Author(s): Kauppila JHK, Baines HL, Bratic A, Simard ML, Freyer C, Mourier A, Stamp C, Filograna R, Larsson NG, Greaves LC, Stewart JB
Publication type: Article
Publication status: Published
Journal: Cell Reports
Online publication date: 13/09/2016
Acceptance date: 11/08/2016
Date deposited: 24/10/2016
ISSN (electronic): 2211-1247
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