Transgenic mice Cre-dependently expressing mutant polymerase-gamma: novel test-system for pharmacological study of mitoprotective drugs

Introduction: PolG-alpha is a nuclear-encoded enzyme which provides replication and repair of mitochondrial DNA. D257A mutation leads to change in the N-terminal ”proofreading” domain, deprives 3?-5? exonuclease activity, resulting accumulation mutations genome.
 Materials methods: Murine zygotes were microinjected with transgene construction carrying mutant murine Polg coding sequence GFP by loxP-flanked STOP-cassette. Two Cre-activator strains, CMV-Cre (systemic activation) Tie2-Cre (endothelial activation), used for activation transgene. To confirm insertion Cre-dependent transgene, genotyping qPCR copy number measurement performed, fluorescence was assessed.
 Results: primary transgenic animals as founders two lines numbers ~7 ~5. After systemic activation, copies decreases ~1.0 while endothelial specific does not affect tail tissue.
 Discussion: A model spatial control Polgexpression has been developed. our knowledge, this first tissue-specific dysfunction.
 Conclusion: Transgenic mice expressing polymerase-gamma are novel test-system studying biology efficacy mitoprotective drugs.