Autism is a neurodevelopmental disorder of complex etiology. Emerging evidence suggests that low cholesterol levels due to defective cholesterol synthesis may play a role in the pathogenesis of autism or autism spectrum disorder (ASD). Cholesterol biosynthesis is essential for brain development because, in contrast to most other organs, the brain must make its own cholesterol from the early embryonic stage. Thus, deficiency in cholesterol production in the brain during embryogenesis may lead to faulty neurodevelopment. The role of cholesterol in the organization and function of lipid rafts, the specialized structural and functional domains in cell membranes, is a fundamental question in biology. Brain cholesterol biosynthetic defects may lead to disorganization of lipid rafts in developing brain, and cause brain abnormalities. In this study, the investigators will delineate the effects of defective cholesterol synthesis on the organization of lipid rafts in the developing brain and the associated pathophysiological consequences. To address these questions, they will employ the genetic mouse models of 3¿-hydroxysterol-¿24 reductase (Dhcr24) and 3¿-hydroxysterol-¿7 reductase (Dhcr7) deficiencies, because these two models represent disruption of two obligatory pathways of cholesterol synthesis. In order to develop an integrated understanding of lipid raft formation in the developing brain and to identify the potential disease-associated biomarkers and disturbed pathways, the investigators will conduct comprehensive analyses of the raft protein and lipid compositions in Dhcr24-deficient and Dhcr7-deficient brains by quantitative proteomics and lipidomics approaches. The proposed research will help to gain further insight into the mechanisms of the membrane defects caused by disruption of cholesterol biosynthesis, and also will shed new light on the potential role of more subtle abnormalities in cholesterol synthesis in ASD.