Maternal Immune Activation in a Genetic Mouse Model of ASD

ASD 遗传小鼠模型中的母体免疫激活

• 批准号: 8917685
• 负责人: Anna Dunaevsky
• 金额: $ 38.8万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8917685
• 关键词: Affect; Anti-Inflammatory Agents; Anti-inflammatory; Behavior; Behavioral; Brain; Dendritic Spines; Development; Disease; Environmental Risk Factor; Epidemiologic Studies; Etiology; Exhibits; Exposure to; Gene Expression; Genes; Genetic; Genetic Risk; Image Analysis; Immune; Immune System and Related Disorders; Impairment; Infection; Lead; Mediating; Molecular; Mus; Mutant Strains Mice; Mutation; Pathway interactions; Pregnancy; Proteins; Regulation; Rett Syndrome; Risk; Risk Factors; Synapses; Testing; Up-Regulation; Whole-Cell Recordings; autism spectrum disorder; behavioral impairment; brain pathway; disorder risk; genetic risk factor; immune activation; in vivo imaging; insight; mouse model; mutant; neurobehavioral; neuropathology; novel; offspring; postnatal; prenatal exposure; prevent; public health relevance; risk variant

 DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is a diverse disorder that is likely to be caused by a combination of genetic alterations and environmental insult during early development. Studies demonstrate an association between maternal immune activation (MIA) during pregnancy and an increased risk for ASD. Recent development of mouse models for prenatal exposure to maternal immune activation (MIA) show that the challenged offspring demonstrate impaired behaviors relevant to ASD as well as exhibit altered levels of immune proteins. A significant gap exists in understanding how altered immune state interacts with ASD risk genes to result in impaired behaviors. Here we will test the hypothesis altered regulation of MHC1 proteins is a mechanism of convergence for MIA and ASD genetic risk factors. Specifically, we will examine how mutations in mecp2, a gene responsible for the Rett syndrome and also associated with non-Rett ASD cases, interact with MIA. We will, combine behavioral, molecular, electrophysiological and synaptic in vivo imaging analyses in relevant brain circuits to determine how altered Mecp2 levels and MIA converge to results in altered behavior and neuropathology.