Expression of the tuberous sclerosis complex gene products, hamartin and tuberin, in central nervous system tissues

Tuberous sclerosis complex (TSC) is a common genetic disorder in which affe cted individuals can develop mental retardation, developmental brain defect s, and seizures. Two genetic loci are responsible for TSC: TSC1 on chromoso me 9q and TSC2 on chromosome 16p. Here, we report our analysis of TSC1 (ham artin) and TSC2 (tuberin) protein expression in the central nervous system (CNS). Both tuberin and hamartin are expressed in neurons and astrocytes wh ere they physically interact. In the mouse cerebellum in vivo, tuberin pred ominantly localizes to the perinuclear region of the Purkinje cell, whereas hamartin is distributed along neuronal or astrocytic processes. In contras t, both hamartin and tuberin demonstrate similar neuronal expression patter ns in pure neuronal cultures in vitro. Additionally, hamartin is highly exp ressed in astrocytes in mixed neuron-glia cultures in vitro, suggesting tha t hamartin may be important for astrocyte growth control. Unlike tuberin, l oss of hamartin expression was not observed in sporadic astrocytomas. These results suggest that tuberin and hamartin may differentially contribute to the CNS pathology in TSC.