Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter.
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.
Liu
Hongyan
H
Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021, USA.
Kishi
Toshiro
T
Roseberry
Aaron G
AG
Cai
Xiaoli
X
Lee
Charlotte E
CE
Montez
Jason M
JM
Friedman
Jeffrey M
JM
Elmquist
Joel K
JK
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology; D022202:Chromosomes, Artificial, Bacterial; D015870:Gene Expression / Q000502:physiology*; D049452:Green Fluorescent Proteins; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D008024:Ligands; D008164:Luminescent Proteins / Q000096:biosynthesis* / Q000235:genetics; D008526:Medulla Oblongata / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000096:biosynthesis / Q000235:genetics*; D014630:Vagus Nerve / Q000378:metabolism
D008024:Ligands; D008164:Luminescent Proteins; D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D049452:Green Fluorescent Proteins