Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice
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...
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1998
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_02706474_v18_n17_p6631_Young https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_02706474_v18_n17_p6631_Young_oai |
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I28-R145-paper_02706474_v18_n17_p6631_Young_oai2024-08-16 Young, J.I. Otero, V. Cerdán, M.G. Falzone, T.L. Cheng Chan, E. Low, M.J. Rubinstein, M. 1998 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. Fil:Young, J.I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Otero, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Cerdán, M.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Falzone, T.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. application/pdf http://hdl.handle.net/20.500.12110/paper_02706474_v18_n17_p6631_Young info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar J. Neurosci. 1998;18(17):6631-6640 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 Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_02706474_v18_n17_p6631_Young_oai |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-145 |
| collection |
Repositorio Digital de la Universidad de Buenos Aires (UBA) |
| topic |
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 |
| spellingShingle |
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 Young, J.I. Otero, V. Cerdán, M.G. Falzone, T.L. Cheng Chan, E. Low, M.J. Rubinstein, M. Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice |
| topic_facet |
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 |
| description |
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. |
| format |
Artículo Artículo publishedVersion |
| author |
Young, J.I. Otero, V. Cerdán, M.G. Falzone, T.L. Cheng Chan, E. Low, M.J. Rubinstein, M. |
| author_facet |
Young, J.I. Otero, V. Cerdán, M.G. Falzone, T.L. Cheng Chan, E. Low, M.J. Rubinstein, M. |
| author_sort |
Young, J.I. |
| title |
Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice |
| title_short |
Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice |
| title_full |
Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice |
| title_fullStr |
Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice |
| title_full_unstemmed |
Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice |
| title_sort |
authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice |
| publishDate |
1998 |
| url |
http://hdl.handle.net/20.500.12110/paper_02706474_v18_n17_p6631_Young https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_02706474_v18_n17_p6631_Young_oai |
| work_keys_str_mv |
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| _version_ |
1809357093245812736 |