Developing Chimeric Animals to Study the Role of Mitochondrial DNA

  • Research tool to understand the role of mitochondrial DNA’s role in diseases and disorders
  • Method to generate Mitochondrial-Nuclear eXchange (MNX) mice
  • Platform to advance personalized medicine

Abstract

Although conventionally it was believed that nuclear DNA (nDNA) primarily determines an individual’s degree of susceptibility to diseases and disorders, in recent years there have been numerous studies that have illustrated that mitochondrial DNA (mtDNA) mutations are a common cause of genetic disease with pathogenic mtDNA mutations. However, currently in the field, there is a lack of ideal preclinical model to study mechanisms of mtDNA disease as well as mitochondria-nuclear interaction. Dr. Ballinger and collaborators have developed methods for inserting nDNA into cells with different types of mtDNA, creating animals with “swapped” nDNA and mtDNA, as well as methods for studying the effects of such DNA swapping.The method of mitochondrial-nuclear exchange involves enucleating two cells and interchanging the nuclei, introducing them into cells with mtDNA with which they are not usually associated. MNX mice provide a platform for studying the role that both the nuclear andmtDNAplay in the susceptibility to diseases and disorders, based specifically on the mitochondrion’s communication with the nucleus (and vice versa). This technology also includes methods of evaluating the effects of such mitochondrial-nuclear exchange, particularly as it relates to mtDNA. Current data suggest that mtDNA plays a much larger role in disease susceptibility and pathogenesis than previously believed, as the mice havesusceptibilities based upon their mtDNA-nDNA combination rather than either genome alone.MNX mice have been successfully utilized to study acute cardiac volume overload, non-alcoholic fatty liver disease, understanding whole body metabolism, adiposity, geneexpressionand pulmonary development.

Potential Applications

About 1 in 4,000 children in the United States will develop mitochondrial disease by the age of 10 years. Up to 4,000 children per year in the US are born with a type of mitochondrial disease.

mtDNA abberations have been implicated in conditions like cardiovascular diseases, cancer, diabetes, musculoskeletal, neurodegenerative, obesity, fitness.

Contact Information

Name: Karen F. Bernard

Email: kbernard@uab.edu

Phone: (205) 934-8826