Genetics, Vol. 177, 2031-2037, December 2007, Copyright © 2007
doi:10.1534/genetics.107.081026

Deletion-Mutant mtDNA Increases in Somatic Tissues but Decreases in Female Germ Cells With Age

Akitsugu Sato*,{dagger},1, Kazuto Nakada*,{ddagger}, Hiroshi Shitara{dagger}, Atsuko Kasahara*,{ddagger}, Hiromichi Yonekawa{dagger} and Jun-Ichi Hayashi*

* Graduate School of Life and Environmental Sciences, {ddagger} Center for Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Ibaraki 305-8572, Japan and {dagger} Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

1 Corresponding author: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1Tennoudai, Tsukuba, Ibaraki 305-8572, Japan.
E-mail: asato{at}biol.tsukuba.ac.jp

The proportions of mutant and wild-type mtDNA are crucial in determining the severity of mitochondrial diseases. It has been generally considered that deletion-mutant mtDNA has replication advantages and accumulates with time. Here, we examine the tissue-by-tissue proportions of mutant mtDNA with a 4696-bp deletion ({Delta}mtDNA) and wild-type mtDNA in mitochondrial disease model mice (mito-mice). Comparison of the proportions of {Delta}mtDNA in each tissue at various ages showed that the rate of accumulation of {Delta}mtDNA differed among tissues. The heart, skeletal muscles, kidney, liver, testis, and ovary showed increases in the proportion of {Delta}mtDNA with age, but the pancreas, spleen, brain, and blood showed only a slight or no increase in proportion. In contrast to the somatic tissues, however, the germ cells of female mito-mice and resultant offspring showed a strong decrease in {Delta}mtDNA with maternal age. The decrease was so acute that some offspring showed complete disappearance of {Delta}mtDNA, even though their elder brothers and sisters had high proportions of {Delta}mtDNA. Female germ cells have a machinery that prevents the inheritence of defective mtDNA to the following generation since germ cells are kept for a long time until they are ovulated.