title: Absence of allelic loss in cytomegalic neurons of cortical tuber in the Eker rat model of tuberous sclerosis.
abstract: The Eker rat is an animal model of tuberous sclerosis caused by a mutation in the Tsc2 gene encoding a tumor suppressor protein, tuberin. According to Knudson's two-hit theory, renal carcinomas and other tumors develop in various organs. Although the incidence of brain lesions is lower in the Eker rat than in human tuberous sclerosis, a cortical tuber was recently found in the cerebrum of an Eker carrier. In this study, we examined whether neuronal cytomegaly in the Eker rat tuber is caused by deletion of the normal Tsc2 allele and resultant loss of tuberin, as is the case with the majority of renal carcinomas. A combination of laser capture microdissection and semi-nested polymerase chain reaction demonstrated the presence of the wild-type Tsc2 allele in the cytomegalic neurons isolated individually. Immunohistochemistry also detected positive tuberin immunoreactivity in many of these giant neurons. These findings were in sharp contrast to those of renal carcinoma cells deriving from allelic loss. Our results provide evidence that many if not all cytomegalic neurons of a cortical tuber occur in the absence of allelic loss.
authors.affiliation: Department of Pediatrics, Jichi Medical School, Tochigi, 3, 311-1 Yakushiji, Minamikawachi, Kawachi-gun, 329-0498, Tochigi, Japan. mmizuguc@jichi.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Masato
authors.initials: M
authors.lastname: Mori
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Mariko Y
authors.initials: MY
authors.lastname: Momoi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Itoh
authors.forename: Sachio
authors.initials: S
authors.lastname: Takashima
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D016147:Genes, Tumor Suppressor; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D009154:Mutation; D009474:Neurons / Q000473:pathology*; D016133:Polymerase Chain Reaction; D051381:Rats; D011922:Rats, Mutant Strains; D012097:Repressor Proteins / Q000235:genetics*; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000473:pathology; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D012097:Repressor Proteins; C000624653:TSC2 protein, human; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins