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Publication : Transcriptional regulation of agouti-related protein (Agrp) in transgenic mice.

First Author  Kaelin CB Year  2004
Journal  Endocrinology Volume  145
Issue  12 Pages  5798-806
PubMed ID  15345681 Mgi Jnum  J:95778
Mgi Id  MGI:3527322 Doi  10.1210/en.2004-0956
Citation  Kaelin CB, et al. (2004) Transcriptional regulation of agouti-related protein (Agrp) in transgenic mice. Endocrinology 145(12):5798-806
abstractText  Agouti-related protein (Agrp) encodes a hypothalamic neuropeptide that promotes positive energy balance by stimulating food intake and reducing energy expenditure. Agrp expression in the brain is restricted to neurons within the arcuate nucleus of the hypothalamus, and expression levels are elevated as a consequence of food deprivation. We tested a series of bacterial artificial chromosome reporter constructs with varying amounts of sequence flanking the Agrp transcription unit in transgenic mice to identify and refine a region of DNA capable of recapitulating characteristics of Agrp expression. We report that a 42.5-kb region upstream of Agrp, containing three distinct regions that are evolutionarily conserved between mouse and human, is necessary and sufficient to consistently drive reporter expression specifically within AgRP neurons in a fasting-responsive manner. In addition, we demonstrate that this region allows for the stable expression of Cre recombinase in transgenic mice, providing a genetic tool for studying anabolic neural circuits that control energy balance.
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