Autism is a complex neurodevelopmental disorder characterized by deficits in social communication, problems in reciprocal social interaction, and repetitive, patterned behavior. While autism is predicted to have a strong genetic basis, the recent increase in the incidence of autism cases suggests that environmental factors may also play a role. The widespread use of persistent organic pollutant polybrominated diphenyl ethers (PBDEs) as commercial flame retardants over the past decade has raised concerns about human exposure to this new pollutant and their potential effects on the developing brain because it bioaccumulates in lipid-rich tissues such as brain. This study was designed to examine the interaction effects of perinatal exposure to brominated diphenyl ether 47 (BDE-47) and genetic susceptibility of an epigenetic pathway on cognitive and social behaviors in a mouse model for Rett Syndrome, one of several autism-spectrum neurodevelopmental disorders with a known genetic cause involving epigenetic pathways. BDE-47 treatment resulted in a long-lived effect on adult spatial learning that was compounded specifically in females heterozygous for the X-linked mutation Mecp2 308 . Mecp2 308/+ female mice were therefore examined for differences in X chromosome inactivation (XCI) ratios. While vehicle control Mecp2 308/+ mice XCI skewed towards expression of wildtype Mecp2 , BDE-47 exposed Mecp2 308/+ mice were more variable in XCI patterns with more mice showing unfavorably skewed XCI which correlated with the behavioral phenotype of poor spatial learning and memory. Therefore, the combination of a genetic risk factor and perinatal exposure of a common organic pollutant showed a long-lived compounding effect on spatial learning behavior of female offspring correlating with epigenetic differences in X chromosome inactivation.
|Advisor:||LaSalle, Janine M.|
|Commitee:||Berman, Robert F., Chedin, Frederic L.|
|School:||University of California, Davis|
|School Location:||United States -- California|
|Source:||MAI 49/04M, Masters Abstracts International|
|Keywords:||Autism, Epigenetics, Mouse behavior, PBDE, Rett syndrome, X chromosome inactivation|
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