MECP2 和有机污染物在神经发育中的表观遗传相互作用-猫眼课题宝

MECP2 和有机污染物在神经发育中的表观遗传相互作用

批准号：

7918624

负责人：

Janine M LaSalle

金额：

$6.72万

依托单位：

UNIVERSITY OF CALIFORNIA AT DAVIS

依托单位国家：

美国

项目类别：

财政年份：

2009

资助国家：

美国

项目状态：

已结题

起止时间：

2009-09-17 至 2010-09-16

来源：

https://reporter.nih.gov/project-details/7918624

关键词：

Address Affect Animal Model Animals Autistic Disorder Behavior Behavioral Binding Proteins Blood Blood specimen Brain Cell Culture Techniques Cells Child Cognition Complex Congenital Rubella Syndrome Defect Detection Development Developmental Delay Disorders Diagnosis Diagnostic Dose Embryonic Development Engineering Environment Environmental Pollutants Environmental Risk Factor Epigenetic Process Ethers Etiology Exposure to Flurothyl Generations Genes Genetic Genetic Predisposition to Disease Genome Genomic Imprinting Genotype Heritability Human Human Milk Individual Infant Learning Link Malignant Neoplasms Measures Meiosis Memory Mental Retardation Methylation Monozygotic Twinning Monozygotic twins Motor Mus Mutation Neuroblastoma Neurodevelopmental Disorder Pentylenetetrazole Perinatal Perinatal Exposure Play Polychlorinated Biphenyls Population Prader-Willi Syndrome Predisposition Prevalence Public Health Rattus Research Personnel Rett Syndrome Risk Rodent Role Sampling Seizures Series Severities Social Behavior Symptoms System Testing Tissues Toxic Environmental Substances X Inactivation Xq28 base behavior test bioaccumulation disorder risk histone modification human disease imprint improved in utero mouse model mutant mouse model neurodevelopment neuropsychological next generation offspring peripheral blood phenyl ether pollutant prenatal programs pup research study

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描述（由申请人提供）：

英文摘要

DESCRIPTION (provided by applicant): Epigenetic mechanisms act at the interface between genetics and environment and are an important determinant in disease risk to complex human diseases such as cancer or autism. This proposal employs a combination of systems and approaches that focus on the central question of the impact of persistent environmental pollutants (POPs) on precise epigenetic changes that occur in neurodevelopmental disorders. The widespread prevalence of POPs such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in the environment and their detection in human milk has prompted concern about in utero and early infant exposure to these compounds. Perinatal exposure to PCBs and PBDEs in rats results in long-lasting defects in learning, memory, behavior, and seizure susceptibility in adulthood. Epigenetic changes to the genome as a result of PCB and PBDE exposures have not been previously explored but are a plausible explanation for the long-lasting effects on neuropsychological function. This proposal will focus specifically on two compounds, PCB 95 and PBDE 47, with high levels in humans and known effects on neurodevelopment. The genetically controlled component of the proposed studies will be to use a genetically engineered Mecp2 mutant mouse model of Rett syndrome and autism. In additional to animal studies, human blood and post-mortem brain samples from individuals with autism, mental retardation, and controls will be tested for precise epigenetic changes in three neurodevelopmentally important genes (MECP2, GABRB3, UBE3A). Since PCB and PBDE levels will be determined in these human samples, correlations of exposures to epigenetic changes can be performed. Several public health relevant questions will be addressed by these studies: What specific epigenetic changes to neurodevelopmentally important genes occur as a result of POP exposure? What is the compounding effect of known genetic and environmental factors in the etiology of autism and mental retardation? Can specific epigenetic changes be diagnostic for autism and mental retardation of unknown genetic etiology? Are epigenetic changes affecting neurodevelopment heritable?

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