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 Citations (Scopus)

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 1 2004

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Agouti-Related Protein
Transgenic Mice
Bacterial Artificial Chromosomes
Neurons
Food Deprivation
Arcuate Nucleus of Hypothalamus
Neuropeptides
Energy Metabolism
Fasting
Eating
DNA
Brain

ASJC Scopus subject areas

  • Endocrinology

Cite this

Transcriptional regulation of Agouti-related protein (Agrp) in transgenic mice. / Kaelin, Christopher B.; Xu, Allison Wanting; Lu, Xin Yun; Barsh, Gregory S.

In: Endocrinology, Vol. 145, No. 12, 01.12.2004, p. 5798-5806.

Research output: Contribution to journalArticle

Kaelin, Christopher B. ; Xu, Allison Wanting ; Lu, Xin Yun ; Barsh, Gregory S. / Transcriptional regulation of Agouti-related protein (Agrp) in transgenic mice. In: Endocrinology. 2004 ; Vol. 145, No. 12. pp. 5798-5806.
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