Mutations in one of two genes, TSC1 and TSC2, result in a similar disease 
phenotype by disrupting the normal interaction of their protein products, 
hamartin and tuberin, which form a functional signaling complex. Disruption of 
these genes in the brain results in abnormal cellular differentiation, 
migration, and proliferation, giving rise to the characteristic brain lesions of 
tuberous sclerosis complex (TSC) called cortical tubers. The most devastating 
complications of TSC affect the central nervous system and include epilepsy, 
mental retardation, autism, and glial tumors. Relevant animal models, including 
conventional and conditional knockout mice, are valuable tools for studying the 
normal functions of tuberin and hamartin and the way in which disruption of 
their expression gives rise to the variety of clinical features that 
characterize TSC. In the future, these animals will be invaluable preclinical 
models for the development of highly specific and efficacious treatments for 
children affected with TSC.