Abstract
Abstract : The specific aims of this concept award are 1) to conduct a battery of behavioral tests on a cerebellar mouse model of Tuberous sclerosis complex to determine whether Tsc2 mediated Purkinje cell loss induces ASD-like deficits; and 2) to determine whether rapamycin, an mTORC1 inhibitor, rescues the Purkinje cell degeneration and behavioral deficits in mutant mice. Here we report substantial progress on Aim 1. We have performed the battery of behavioral tests on the cerebellar mouse model of TSC. Here we demonstrate that mild social deficits occur in a Tsc2 haploinsufficient environment and are exacerbated by loss of Purkinje cells. Purkinke cell loss leads to repetitive behavior. Autistic-like behaviors are more severe in male Tsc2f/-;Cre mice than female mice. We have also submitted out findings to the Neurobiology of Disease for review.
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