Examining rescue of neurological deficits in Angelman syndrome mice by expression of the E6-AP isoforms

$84,011

In this study, Dr. Dindot plans to investigate whether gene therapy in the AS mouse (using lentiviruses as the vector) is a viable therapeutic option, and thus a future possibility for individuals with AS. He will also examine the function of the E6-AP (UBE3A) isoforms. He will use live animal testing of brain function and cell morphological studies in a mouse model of AS to determine if gene therapy can ameliorate the neurological deficits exhibited by these mice. This proposal will examine two unresolved questions regarding gene therapy in AS. First, he will examine whether re-introduction of UBE3A expression into the brain of post-adolescent and adult mice rescues abnormal neuronal morphology, reduces seizures, enhances learning and memory, and improves motor-coordination. Second, he will examine the efficacy of the 3 E6-AP isoforms to improve brain function in AS mice with the intent of identifying a particular isoform that can be used in gene therapy studies.