Role of Mitochondrial DNA Mutations in Cellular Vulnerability to Mitochondria-Specific Environmental Toxins
Abstract
In recent years, growing evidence has shown that mutations of mitochondrial DNA (mtDNA) are an important cause of mitochondrial disorders in humans, and have been associated with common neurodegenerative disorders, aging and cancers. In line with this, it has been proposed that those mutations could genetically predispose an individual to some environmental factors thereby initiating the disease process. To test such a hypothesis in Parkinson's disease we proposed to: 1) develop an animal model with accumulated mtDNA mutations in catecholaminergic neurons by creating a transgenic mouse containing a tyrosine hydroxylase (TH) promoter-driven transgene encoding a proofreading-deficient mouse mtDNA polymerase (Pol gamma), 2) testing whether those animals are more susceptible to mitochondria-specific environmental toxins and aging 3) investigating the underlined molecular mechanism. In this annual report, we describe the characterization of a transgenic mouse line which produces at high level a proofreading-deficient mouse mtDNA polymerase (pol gamma) in TH expressing tissues at different developmental stages (from embryogenesis to adult). Then, we describe the strategy that we are currently using to perform a sequence analysis of the mtDNA isolated from the ventral mesencephalon of transgenic animals. This study should tell us whether mtDNA mutations accumulate in catecholaminergic tissues in this experimental model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2005
- Accession Number
- ADA436888
Entities
People
- Etienne C. Hirsch
Organizations
- French National Institute of Health and Medical Research