Artículo
Abstract:
The pro-opiomelanocortin (POMC) gene is expressed in a subset of hypothalamic and hindbrain neurons and in pituitary melanotrophs and corticotrophs. POMC neurons release the potent opioid β-endorphin and several active melanocortins that control homeostasis and feeding behavior. POMC gene expression in the CNS is believed to be controlled by distinct cis- acting regulatory sequences. To analyze the transcriptional regulation of POMC in neuronal and endocrine cells, we produced transgenic mice carrying POMC27*, a transgene containing the entire 6 kb of the POMC transcriptional unit together with 13 kb of 5' flanking regions and 8 kb of 3' flanking regions: POMC27* was tagged with a heterologous 30 bp oligonucleotide in the third exon. In situ hybridization studies showed an accurate cell-specific pattern of expression of POMC27* in the arcuate nucleus and the pituitary. Hypothalamic mRNA-positive neurons colocalized entirely with β-endorphin immunoreactivity. No ectopic transgenic expression was detected in the brain. Deletional analyses demonstrated that neuron-specific expression of POMC transgenes required distal 5' sequences localized upstream of the pituitary- responsive proximal cis-acting elements that were identified previously. POMC27* exhibited a spatial and temporal pattern of expression throughout development that exactly paralleled endogenous POMC. RNase protection assays revealed that POMC27* expression mimicked that of POMC in different areas of the CNS and most peripheral organs with no detectable ectopic expression. Hormonal regulation of POMC27* and POMC was identical in the hypothalamus and pituitary. These results show that distal 5' sequences of the POMC gene located between -13 and -2 kb target expression into the CNS of transgenic mice in a precise neuron-specific, developmentally and hormonally regulated manner.
Registro:
| Documento: | Artículo |
| Título: | Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice |
| Autor: | Young, J.I.; Otero, V.; Cerdán, M.G.; Falzone, T.L.; Cheng Chan, E.; Low, M.J.; Rubinstein, M. |
| Filiación: | Inst. de Invest. en Ingenleria G., Univ. de Buenos Aires-Consejo N., 1428 Buenos Aires, Argentina Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, United States Depto. de Quim. Biológica, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina Inst. de Invest. en Ing. Genet. y B., Consejo Nac. de Invest. Cie. y Tec., Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina Endocrine Unit, John Hunter Hospital, Newcastle, NSW, Australia |
| Palabras clave: | β- endorphin; Arcuate nucleus; Gene expression; Hypothalamus; Melanocortin; Neuron-specific expression; Pituitary; Pro-opiomelanocortin; Transgenic mice; melanocortin; animal cell; animal experiment; animal tissue; article; cell specificity; gene amplification; gene deletion; gene expression regulation; gene library; gene location; genome; hormonal regulation; hypothalamus; in situ hybridization; nonhuman; plasmid; polymerase chain reaction; priority journal; rhombencephalon; transgenic mouse; Animals; DNA Fragmentation; Gene Expression Regulation, Developmental; Genome; Hypothalamus; Mice; Mice, Transgenic; Neurons; Organ Specificity; Pro-Opiomelanocortin; Rhombencephalon |
| Año: | 1998 |
| Volumen: | 18 |
| Número: | 17 |
| Página de inicio: | 6631 |
| Página de fin: | 6640 |
| Título revista: | Journal of Neuroscience |
| Título revista abreviado: | J. Neurosci. |
| ISSN: | 02706474 |
| CODEN: | JNRSD |
| CAS: | Pro-Opiomelanocortin, 66796-54-1 |
| PDF: | https://bibliotecadigital.exactas.uba.ar/download/paper/paper_02706474_v18_n17_p6631_Young.pdf |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v18_n17_p6631_Young |
Referencias:
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Citas:
---------- APA ----------
Young, J.I., Otero, V., Cerdán, M.G., Falzone, T.L., Cheng Chan, E., Low, M.J. & Rubinstein, M. (1998) . Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice. Journal of Neuroscience, 18(17), 6631-6640.Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v18_n17_p6631_Young [ ]
---------- CHICAGO ----------
Young, J.I., Otero, V., Cerdán, M.G., Falzone, T.L., Cheng Chan, E., Low, M.J., et al. "Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice" . Journal of Neuroscience 18, no. 17 (1998) : 6631-6640.Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v18_n17_p6631_Young [ ]
---------- MLA ----------
Young, J.I., Otero, V., Cerdán, M.G., Falzone, T.L., Cheng Chan, E., Low, M.J., et al. "Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice" . Journal of Neuroscience, vol. 18, no. 17, 1998, pp. 6631-6640.Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v18_n17_p6631_Young [ ]
---------- VANCOUVER ----------
Young, J.I., Otero, V., Cerdán, M.G., Falzone, T.L., Cheng Chan, E., Low, M.J., et al. Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice. J. Neurosci. 1998;18(17):6631-6640.Available from: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v18_n17_p6631_Young [ ]
