A Mouse Model of Mitochondrial Disease Reveals Germline Selection Against Severe MtDNA Mutations

Overview

Journal Science

Specialty Science

Date 2008 Feb 16

PMID 18276892

Citations 220

Authors

Weiwei Fan

Katrina G Waymire

Navneet Narula

Peng Li

Christophe Rocher

Pinar E Coskun

Mani A Vannan

Jagat Narula

Grant R MacGregor

Douglas C Wallace

Affiliations

Soon will be listed here.

Abstract

The majority of mitochondrial DNA (mtDNA) mutations that cause human disease are mild to moderately deleterious, yet many random mtDNA mutations would be expected to be severe. To determine the fate of the more severe mtDNA mutations, we introduced mtDNAs containing two mutations that affect oxidative phosphorylation into the female mouse germ line. The severe ND6 mutation was selectively eliminated during oogenesis within four generations, whereas the milder COI mutation was retained throughout multiple generations even though the offspring consistently developed mitochondrial myopathy and cardiomyopathy. Thus, severe mtDNA mutations appear to be selectively eliminated from the female germ line, thereby minimizing their impact on population fitness.

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