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Expression of Rattus norvegicus mtDNA in Mus musculus cells results in multiple respiratory chain defects

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posted on 2000-10-06, 00:00 authored by Matthew McKenzieMatthew McKenzie, I Trounce
The production of in vitro and in vivo models of mitochondrial DNA (mtDNA) defects is currently limited by a lack of characterized mouse cell mtDNA mutants that may be expected to model human mitochondrial diseases. Here we describe the creation of transmitochondrial mouse (Mus musculus) cells repopulated with mtDNA from different murid species (xenomitochondrial cybrids). The closely related Mus spretus mtDNA is readily maintained when introduced into M. musculus mtDNA-less (ρ) cells, and the resulting cybrids have normal oxidative phosphorylation (OXPHOS). When the more distantly related Rattus norvegicus mtDNA is transferred to the mouse nuclear background the mtDNA is replicated, transcribed, and translated efficiently. However, function of several OXPHOS complexes that depend on the coordinated assembly of nuclear and mtDNA-encoded proteins is impaired. Complex I activity in the Rattus xenocybrid was 46% of the control mean; complex III was 37%, and complex IV was 78%. These defects combined to restrict maximal respiration to 12-31% of the control and M. spretus xenocybrids, as measured polarographically using isolated cybrid mitochondria. These defects are distinct to those previously reported for human/primate xenocybrids. It should be possible to produce other mouse xenocybrid constructs with less severe OXPHOS phenotypes, to model haman mtDNA diseases.

History

Journal

Journal of Biological Chemistry

Volume

275

Issue

40

Pagination

31514 - 31519

Publisher

American Society for Biochemistry and Molecular Biology

Location

Bethesda, MD

ISSN

0021-9258

Language

eng

Publication classification

CN.1 Other journal article