UC San Diego

Aicardi-Goutières Syndrome is a neurological disease resulting in a variable array of symptoms, of which include microcephaly, calcification of the basal ganglia, leukodystrophy, and other neurological defects, all of which are accompanied by a mild to severe mental handicap seen in patients with the disease. In this disease, there is a mishandling of nucleic acids due to mutations in one of several nucleases and this mishandling is hypothesized to be involved in an autoimmune response triggered by the anomalous DNA or RNA. In order to better study the effects of these mutations, in particular mutations in three-prime repair exonuclease 1 (TREX1), I have described a method to generate neural progenitor cells, neurons, and astrocytes from induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) to obviate the need to isolate brain tissue from patients or utilize post-mortem brain tissue. By reprogramming AGS1 patient fibroblasts with a V201D mutation into iPSCs and by generating H9 embryonic stem cell wild-type/mutant TREX1 isogenic pairs, along with being able to successful differentiate these pluripotent stem cells into cells of the neural lineage, I have begun to establish an in vitro platform that allows for direct observation of the effects of TREX1 mutations on the development and function of various cell types that make up the brain