Co-localization of TSC1 and TSG2 gene products in tubers of patients with tuberous sclerosis

Two genes, mutations in which result in the phenotype of tuberous sclerosis (TSC), have recently been cloned. TSC2 on chromosome 16p13.3 encodes the p rotein tuberin, which appears to have growth regulating properties, TSC1 on chromosome 9q34 encodes hamartin which, as yet, has no specified cellular functions, Polyclonal antibodies were raised to synthetic peptides represen ting portions of tuberin and hamartin and used in immunoblots and immunohis tochemical studies to localize the proteins in surgically resected neocorti cal tubers from four TSC patients. On Western blots of autopsy brain specim ens, K-562 cell, and NT2 lysates, each antibody labelled a single band at t he expected molecular weight, In immunohistochemical protocols on paraffin embedded tissue, antibodies to both tuberin and hamartin prominently labell ed atypical and dysmorphic neuroglial cells that are a defining feature of TSC tubers, Some abnormal cells within cortical tuber sections were labelle d with both tuberin and hamartin antisera, Our results suggest that tuberin and hamartin are both robustly expressed in similar populations of neurogl ial cells of TSC tubers, even in the presence of TSC1 or TSC2 germline muta tions, The roles of these gene products in normal and abnormal cortical dev elopment, tuber pathogenesis and the generation of seizures remain to be de fined.