Stem Cell Models to Investigate the Role of DNA Methylation Machinery in Development of Neuropsychiatric Disorders

Figure 2

Schematic representation generation of embryonic stem cell-based models for studying the role of DNMT dysregulation on development of abnormal neuronal phenotypes. Desired mutations can be selected on the basis of literature evidence of mutations in DNMTs that are associated with neuropsychiatric disorders. Both alleles of DNMTs (de novo and maintenance) can be targeted to introduce desired mutations in the wild-type ES cells. First round of targeting results in heterozygotes which can then be used for a second round of targeting that results in homozygotes. Following gene targeting, homozygous ESCs (for recessive mutations) or heterozygous ESCs (for dominant mutations) can be differentiated into neurons. The resultant neurons can be used for detailed physiological and molecular-genetic studies to identify the molecular basis for abnormal neuronal phenotypes.