TY - JOUR
T1 - Expression of the tuberous sclerosis 2 gene product, tuberin, in adult and developing nervous system tissues
AU - Geist, Robert T.
AU - Reddy, Anita J.
AU - Zhang, Jie
AU - Gutmann, David H.
N1 - Funding Information:
The first two authors contributed equally. We appreciate the technical assistance of Mick Hunter and Dr. Michael J. Giordano as well as the advice of Dr. Anne Fagan-Niven during the execution of this project. We gratefully acknowledge the generosity of Drs. Jeff DeClue and Ralf Wienecke for providing their tuberin antibodies for comparison studies. DHG is supported by a grant from the National Tuberous Sclerosis Association.
PY - 1996/4
Y1 - 1996/4
N2 - Tuberous sclerosis (TS) is an autosomal dominant disorder in which affected individuals manifest mental retardation, seizures, and a variety of benign and malignant tumors. The TSC2 tumor suppressor gene was recently identified by positional cloning and its protein product, tuberin, 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 TS, we examined the expression of tuberin in adult and developing nervous system tissues. Since tuberin is the second rapGAP found in the nervous 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 opposed to rapGAP, which is not enriched in these tissues. Tuberin expression in the adult CNS is restricted to the olfactory bulb, several CNS neuronal populations, brainstem nuclei, cerebellar Purkinje cells, and motor neurons in the ventral spinal cord. In contrast, rapGAP is expressed in many different cell types in the adult CNS, but not in cerebellar Purkinje cells or motor neurons in the ventral spinal cord. However, there is significant expression of rapGAP in astrocytes. The restricted distribution of tuberin expression relative to rap1 and rapGAP suggests that tuberin may be the primary rap1 regulator in a subpopulation of CNS neurons.
AB - Tuberous sclerosis (TS) is an autosomal dominant disorder in which affected individuals manifest mental retardation, seizures, and a variety of benign and malignant tumors. The TSC2 tumor suppressor gene was recently identified by positional cloning and its protein product, tuberin, 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 TS, we examined the expression of tuberin in adult and developing nervous system tissues. Since tuberin is the second rapGAP found in the nervous 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 opposed to rapGAP, which is not enriched in these tissues. Tuberin expression in the adult CNS is restricted to the olfactory bulb, several CNS neuronal populations, brainstem nuclei, cerebellar Purkinje cells, and motor neurons in the ventral spinal cord. In contrast, rapGAP is expressed in many different cell types in the adult CNS, but not in cerebellar Purkinje cells or motor neurons in the ventral spinal cord. However, there is significant expression of rapGAP in astrocytes. The restricted distribution of tuberin expression relative to rap1 and rapGAP suggests that tuberin may be the primary rap1 regulator in a subpopulation of CNS neurons.
UR - http://www.scopus.com/inward/record.url?scp=0030130431&partnerID=8YFLogxK
U2 - 10.1006/nbdi.1996.0011
DO - 10.1006/nbdi.1996.0011
M3 - Article
C2 - 9173918
AN - SCOPUS:0030130431
SN - 0969-9961
VL - 3
SP - 111
EP - 120
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 2
ER -