Immortalization of neuroendocrine pinealocytes from transgenic mice by targeted tumorigenesis using the tryptophan hydroxylase promoter Journal Article


Authors: Son, J. H.; Chung, J. H.; Huh, S. O.; Park, D. H.; Peng, C.; Rosenblum, M. G.; Chung, Y. I.; Joh, T. H.
Article 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.
Keywords: controlled study; nonhuman; mouse; mammalia; animal tissue; gene expression; animal experiment; carcinogenesis; transgenic mouse; animalia; mus musculus; biosynthesis; reporter gene; simian virus 40; dna flanking region; virus t antigen; pineal body tumor; neurosecretory cell; pineal body; cell immortalization; circadian rhythm; simiae; raphe nucleus; simian virus; priority journal; article; tryptophan hydroxylase; serotonin n-acetyltransferase; transgenic pineal tumor; tryptophan hydroxylase promoter; serotonin n acetyltransferase; pinealocyte
Journal Title: Molecular Brain Research
Volume: 37
Issue: 1-2
ISSN: 0169-328X
Publisher: Elsevier B.V.  
Date Published: 1996-04-01
Start Page: 32
End Page: 40
Language: English
DOI: 10.1016/0169-328x(95)00271-s
PUBMED: 8738133
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
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