EXPRESSION OF THE TUBEROUS SCLEROSIS-2 GENE-PRODUCT, TUBERIN, IN ADULT AND DEVELOPING NERVOUS-SYSTEM TISSUES

Tuberous sclerosis (TS) is an autosomal dominant disorder in which aff ected individuals manifest mental retardation, seizures, and a variety of benign and malignant tumors. The TSC2 tumor suppressor gene was re cently identified by positional cloning and its protein product, tuber in, shown to represent one member of the rap GTPase activating protein (rapGAP) family. In order to determine the contribution of tuberin to the development of mental retardation and seizures in patients with T S, we examined the expression of tuberin in adult and developing nervo us system tissues. Since tuberin is the second rapGAP found in the ner vous system, the expression of tuberin was compared to the expression of rapGAP, rap1, and rap2. In this study, we demonstrate that tuberin is expressed at greatest levels in the spinal cord and cerebellum as o pposed to rapGAP, which is not enriched in these tissues. Tuberin expr ession in the adult CNS is restricted to the olfactory bulb, several C NS neuronal populations, brainstem nuclei, cerebellar Purkinje cells, and motor neurons in the ventral spinal cord. In contrast, rapGAP is e xpressed in many different cell types in the adult CNS, but not in cer ebellar Purkinje cells or motor neurons in the ventral spinal cord. Ho wever, there is significant expression of rapGAP in astrocytes. The re stricted distribution of tuberin expression relative to rap1 and rapGA P suggests that tuberin may be the primary rap1 regulator in a subpopu lation of CNS neurons. (C) 1996 Academic Press, Inc.