Transgenic mice with myocardial targeted overexpression of genes encoding proteins for mitochondrial import, phosphorylation, dephosphorylation, and mitochondrial DNA replication.
- Unique in vivo method to elucidate mechanism of AIDS related mitochondrial cardiomyopathy.
- Selective overexpression of both native and mutant genes.
- Ability to assess antiviral compound toxicity.
Survival with AIDS has improved dramatically with the introduction of highly active antiretroviral therapy (HAART). However, one of the major components of this treatment, nucleoside reverse transcriptase inhibitors (NRTIs), induces the development of mitochondrial cardiomyopathy. While there are many existing hypotheses that suggest possible mechanisms by which this condition develops, the actual cause remains unknown. Emory researchers have developed a series of cardiac targeted transgenic mice that will elucidate the contributions of NRTI processing in AIDS related mitochondrial cardiomyopathy. Several mouse models, including those that overexpress genes related to mitochondrial import, phosphorylation, dephosphorylation, and mitochondrial DNA replication are available.
The mouse models and their use in determining NRTI relation to mitochondrial cardiomyopathy has been reduced to practice.