DECREASED PHYSICAL PERFORMANCE OF CONGENIC MICE WITH MISMATCH BETWEENTHE NUCLEAR AND THE MITOCHONDRIAL GENOME

Maternal transmission of mitochondrial DNA (mtDNA) allows us to genera te mtDNA congenic strain by repeating backcrosses of female mice to ma le mice of an inbred strain, which carries different mtDNA haplotype f rom that of the female progenitor. Since genetic backgrounds of inbred strains commonly used (e.g., C57BL/ 6J [B6] and BALB/c) are mainly de rived from an European subspecies of Mus musculus domesticus, congenic strains, in which mtDNA originated from an Asian subspecies M. muscul us musculus or an European species M. spretus, give in vivo condition that mismatch occurs between the mitochondrial and the nuclear genome. So far, little has been known how the mismatch condition affects the physiological phenotype of the mice. To address this question, we esta blished two mtDNA congenic strains, C57BL/6J(BG)-mt(SPR) and BALB/c-mt (SHH), which carry M. spretus-and M. m. musculus-derived mtDNAs, repre senting the conditions of interspecific and intersubspecific mitochond rial-nuclear genome mismatch, respectively. Using these congenic strai ns, we examined their physical performance by measuring their running time on a treadmill belt until exhaustion. The result clearly showed t hat the mtDNA congenic strains manifested a significant decrease in th e level of physical performance, when compared with their progenitor s trains. It also appeared that the congenic mice manifested growth rate . Thus, all results indicated that mismatch between the mitochondrial and the nuclear genome causes phenotypic changes in individuals of mic e.