Production of homoplasmic xenomitochondrial mice

Abstract

The unique features of mtDNA, together with the lack of a wide range of mouse cell mtDNA mutants, have hampered the creation of mtDNA mutant mice. To overcome these barriers mitochondrial defects were created by introducing mitochondria from different mouse species into Mus musculus domesticus (Mm) mtDNA-less (rho(0)) L cells. Introduction of the closely related Mus spretus (Ms) or the more divergent Mus dunni (Md) mitochondria resulted in xenocybrids exhibiting grossly normal respiratory function, but mild metabolic deficiencies, with 2- and 2.5-fold increases in lactate production compared with controls. The transfer of this model from in vitro to in vivo studies was achieved by introducin..