Tuberous Sclerosis Complex (TSC) is an autosomal dominant disorder caused by mutation of the TSC1 or TSC2 gene with an incidence of one in 6,000 births. Patients with TSC have variable numbers of dysplastic foci, known as cortical tubers, in their cerebral cortices, and nearly all patients suffer from seizures and many have autism, mental retardation and/or behavioral disturbances. These cerebral malformations clearly represent defects in brain development, but the pathogenesis of these lesions is not well understood.
Herein is described my investigations into the etiology of cortical tubers and the function of the TSC2 gene product, tuberin, in cortical development through the creation of an RNAi-based model of TSC neuropathology. This is the first model that allows controlled replication of both cellular and histological features of cerebral TSC in vivo. The development of this model will be explained and its features characterized in relation to TSC cerebral pathology and to other models of TSC. Additionally, work using this model to elucidate the etiology of one feature of cerebral TSC, namely cortical dyslamination, will be described and a role for tuberin in neuronal migration demonstrated and explicated.
|Advisor:||Kriegstein, Arnold R.|
|School Location:||United States -- New York|
|Source:||DAI-B 69/10, Dissertation Abstracts International|
|Subjects:||Molecular biology, Neurosciences, Cellular biology|
|Keywords:||Cerebral lesions, Corticogenesis, Migration disorders, Neuronal migraiton, Pathogenesis, Tuberin, Tuberous sclerosis|
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