Transcriptional regulation of Agouti-related protein (Agrp) in transgenic mice

Christopher B. Kaelin, Allison Wanting Xu, Xin Yun Lu, Gregory S. Barsh

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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 AgFp 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 witbin 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 con trol energy balance.

Original languageEnglish (US)
Pages (from-to)5798-5806
Number of pages9
JournalEndocrinology
Volume145
Issue number12
DOIs
StatePublished - Dec 2004

ASJC Scopus subject areas

  • Endocrinology

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