Project Detail
Interagency Autism Coordinating Committee (IACC) logo
Office of Autism Research Coordination (OARC) logo

Toxicant-induced autism and mitochondrial modulation of nuclear gene expression  

Autism has been associated with epigenetic changes: Tiny chemical tags in the regulatory regions of genes that affect how genes express themselves by turning them on or off. One gene often decreased in expression in the brain tissue of autistic individuals is MECP2, a gene that governs the expression of genes crucial to brain development. Exposure to environmental pollutants is also thought to play a role in autism. These two phenomena both involve a small cellular organ called mitochondria. The suspect environmental pollutants are toxic to mitochondria, which play a critical role in epigenetics: Pollution exposure can lower the amount of mitochondrial DNA (mtDNA) in a cell, causing an increase in placement of epigenetic tags by DNMT1 that leads to gene silencing. We hypothesize that exposure during pregnancy to pollutants toxic to mitochondria causes a decrease in mtDNA copy number and increased placement of epigenetic tags by DNMT1 on key developmental genes, affecting pathways that have direct roles in the development of autism. We will expose mice, during pregnancy, to selected toxicants and evaluate adult behavior and associated biochemical changes in brain tissue. Valproic acid will be used as a positive control, with saline as a negative control. The environmental pollutants lead, arsenic, cadmium, manganese, mercury, and permethrin will be investigated for their potential to induce autistic behavior changes. Brain tissue will then be used for molecular studies of mtDNA copy number, expression of DNMT1, and alterations to the epigenome on both a genomewide and gene-specific level. Project Status
ONGOING

2010

Funder Department of Defense
Fiscal Year Funding $0.00
Current Award Period 2009-2010
Project Number AR080091
Principal Investigator Wlodarczyk, Bogdan
Received ARRA Funding? No
Strategic Plan Question Question 3: What Caused This To Happen And Can This Be Prevented? (Causes)
Subcategory Epigenetics
Strategic Plan Objective New! Green dot: Objective has greater than or equal to the recommended funding. 3SJ. Support at least three studies that focus on the role of epigenetics in the etiology of ASD, including studies that include assays to measure DNA methylations and histone modifications and those exploring how exposures may act on maternal or paternal genomes via epigenetic mechanisms to alter gene expression, by 2012. IACC Recommended Budget: $20,000,000 over 5 years.
Federal or Private? Federal
Institution Texas A&M University
State/Country Texas
Web Link 1 Toxicant-induced autism and mitochondrial modulation of nuclear gene expression (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
New! History/Related Projects Toxicant-induced autism and mitochondrial modulation of nuclear gene expression | $0.00 | 2009 | AR080091