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Submitted on July 23, 2004
Accepted on August 26, 2004
Departments of Genetics and Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pharmacology, University of Texas Health Science Center, San Antonio, TX 78229, USA
* To whom correspondence should be addressed. E-mail: gbarsh{at}cmgm.stanford.edu.
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 BAC 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 which 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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