Nuclear Expression of a Mitochondrial DNA Gene: Mitochondrial Targeting of Allotopically Expressed Mutant ATP6 in TransgenicMice

作者：Dunn David A; Pinkert Carl A^*

来源：Journal of Biomedicine and Biotechnology, 2012, 2012: 541245.

DOI：10.1155/2012/541245

Nuclear encoding of mitochondrial DNA transgenes followed by mitochondrial targeting of the expressed proteins (allotopic expression; AE) represents a potentially powerful strategy for creating animal models of mtDNA disease. Mice were created that allotopically express either a mutant (A6M) or wildtype (A6W) mt-Atp6 transgene. Compared to non-transgenic controls, A6M mice displayed neuromuscular and motor deficiencies (wire hang, pole, and balance beam analyses; P %26lt; 0.05), no locomotor differences (gait analysis; P %26lt; 0.05) and enhanced endurance in Rota-Rod evaluations (P %26lt; 0.05). A6W mice exhibited inferior muscle strength (wire hang test; P %26lt; 0.05), no difference in balance beam footsteps, accelerating Rota-Rod, pole test and gait analyses; (P %26lt; 0.05) and superior performance in balance beam time-to-cross and constant velocity Rota-Rod analyses (P %26lt; 0.05) in comparison to non-transgenic control mice. Mice of both transgenic lines did not differ from non-transgenic controls in a number of bioenergetic and biochemical tests including measurements of serum lactate and mitochondrial MnSOD protein levels, ATP synthesis rate, and oxygen consumption (P %26gt; 0.05). This study illustrates a mouse model capable of circumventing in vivo mitochondrial mutations. Moreover, it provides evidence supporting AE as a tool for mtDNA disease research with implications in development of DNA-based therapeutics.

• 出版日期2012