A major goal of regenerative medicine is to generate in vitro models and sources of cell replacements for diseases of the brain and nervous system. These diseases have been particularly difficult to study because it has not been feasible to culture and propagate human neurons from affected individuals. Over the five year course of this grant, many ground breaking discoveries have emerged that will allow researchers to generate human neurons in vitro fro a wide variety of individuals who differ in their disease state or genetic propensity to disease. While this is clearly an exciting prospect, we still do not understand two key features of neurons. First, it is not know why neurons cannot be induced to divide in vitro. Second, neuronal genomes have never been sequenced to determine whether they maintain their integrity over the lifetime of the organism. Here we proposed to test whether neuronal genomes are maintained similarly to other cell types by using somatic cell nuclear transfer to produce clones mice and clones ES cell lines from adult post mitotic neurons. We succeeded at this and have now shown that the genomes of adult most mitotic cortical neurons can produce fertile and viable mice. Further, we performed high resolution genome sequencing of the cell lines derived from these neurons. Remarkably these studies showed that each of three neurons taken from the same adult organism differs from its neighbors in ~80 locations. These data suggest that it will be important to continue these studies on human neurons to ensure that we are developing the most effective models of human disease in a dish.