Authentic cell-specific and developmentally regulated expression of pro- opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice

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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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Detalles Bibliográficos
Autores principales: Young, J.I., Otero, V., Cerdán, M.G., Falzone, T.L., Cheng Chan, E., Low, M.J., Rubinstein, M.
Formato: JOUR
Materias:
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
Mice
Mice, Transgenic
Neurons
Organ Specificity
Pro-Opiomelanocortin
Rhombencephalon
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_02706474_v18_n17_p6631_Young
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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.

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