Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter

Hongyan Liu, Toshiro Kishi, Aaron G. Roseberry, Xiaoli Cai, Charlotte E. Lee, Jason M. Montez, Jeffrey M. Friedman, Joel K. Elmquist

Research output: Contribution to journalArticlepeer-review

305 Scopus citations

Abstract

The melanocortin-4 receptor (MC4-R) is an important regulator of energy homeostasis, and evidence suggests that MC4-R-expressing neurons are downstream targets of leptin action. MC4-Rs are broadly expressed in the CNS, and the distribution of MC4-R mRNA has been analyzed most extensively in the rat. However, relatively little is known concerning chemical profiles of MC4-R-expressing neurons. The extent to which central melanocortins act presynaptically or postsynaptically on MC4-Rs is also unknown. To address these issues, we have generated a transgenic mouse line expressing green fluorescent protein (GFP) under the control of the MC4-R promoter, using a modified bacterial artificial chromosome. We have confirmed that the CNS distribution of GFP-producing cells is identical to that of MC4-R mRNA in wild-type mice and that nearly all GFP-producing cells coexpress MC4-R mRNA. For example, cells coexpressing GFP and MC4-R mRNA were distributed in the paraventricular hypothalamic nucleus (PVH) and the dorsal motor nucleus of the vagus (DMV). MC4-R promotor-driven GFP expression was found in PVH cells producing thyrotropin-releasing hormone and in cholinergic DMV cells. Finally, we have observed that a synthetic MC3/4-R agonist, MT-II, depolarizes some GFP-expressing cells, suggesting that MC4-Rs function postsynaptically in some instances and may function presynaptically in others. These studies extend our knowledge of the distribution and function of the MC4-R. The transgenic mouse line should be useful for future studies on the role of melanocortin signaling in regulating feeding behavior and autonomic homeostasis.

Original languageEnglish (US)
Pages (from-to)7143-7154
Number of pages12
JournalJournal of Neuroscience
Volume23
Issue number18
DOIs
StatePublished - Aug 6 2003

Keywords

  • CRH
  • Choline acetyltransferase
  • Electrophysiological recording
  • GAD67
  • GFP
  • MC4-R
  • Oxytocin
  • TRH
  • Transgenic mouse

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter'. Together they form a unique fingerprint.

Cite this