title: Immortalization of neuroendocrine pinealocytes from transgenic mice by targeted tumorigenesis using the tryptophan hydroxylase promoter.
abstract: Tryptophan hydroxylase (TPH) is the first enzyme in both serotonin and melatonin biosynthesis in neuroendocrine cells of the pineal gland. The lack of immortalized neuroendocrine pineal cell lines has been a major obstacle to the study of the tissue-specific and circadian regulation of TPH gene expression in the pineal gland. Previously, we demonstrated that a 6.1 kb 5' upstream region of the mouse TPH gene directs the restricted expression of a lacZ reporter gene to the pineal gland and the raphe nuclei of transgenic mice. Therefore, to develop TPH-expressing pineal cell lines we first established transgenic mice carrying a construct consisting of 6.1 kb of 5' flanking region fused to the SV40 T-antigen. These animals developed highly invasive pineal tumors and died at 12-15 weeks of age. The pineal tumors obtained from the transgenic mice were utilized to establish the immortalized pinealocyte-derived cell lines. These cells express two marker enzymes, TPH and serotonin N-acetyltransferase (NAT). In pineal gland TPH and NAT expressions have been known to be regulated during circadian cycle. The two established cell lines therefore promise to be a valuable in vitro model system for the study of the rhythmic nature of the pineal function at molecular level in mammal.
authors: Laboratory of Molecular Neurobiology, Cornell University Medical College, W.M. Burke Medical Research Institute, White Plains, NY 10605, USA.
authors: J H
authors: JH
authors: Son
authors: J H
authors: JH
authors: Chung
authors: S O
authors: SO
authors: Huh
authors: D H
authors: DH
authors: Park
authors: C
authors: C
authors: Peng
authors: M G
authors: MG
authors: Rosenblum
authors: Y I
authors: YI
authors: Chung
authors: T H
authors: TH
authors: Joh
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010870:Pineal Gland / Q000502:physiology*; D010871:Pinealoma / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014365:Tryptophan Hydroxylase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D014365:Tryptophan Hydroxylase