Melanin-concentrating hormone receptor subtypes 1 and 2: species-specific gene expression.
To assess the contribution of potential central nervous system pathways implicated in the control of appetite regulation and energy metabolism, it is essential to first identify appropriate animal models. Melanin-concentrating hormone (MCH), a conserved cyclic neuropeptide implicated in the modulation of food intake, has been shown to bind and activate two G-protein-coupled receptors, called GPR24 and MCHR2, expressed in human brain and other tissues. Here we show that several non-human species (rat, mouse, hamster, guinea pig, and rabbit) do not have functional MCHR2 receptors, or encode a nonfunctional MCHR2 pseudogene while retaining GPR24 expression. We identified three species for further evaluation that express both MCH receptor subtypes. We cloned and functionally characterized dog, ferret, and rhesus GPR24 and MCHR2 in mammalian cells and studied their brain distribution patterns by in situ hybridization. The homology, expression profile, and functional similarity of the receptors in the dog, ferret, and rhesus to that of human support the potential use of these species as preclinical animal models in the development of therapeutic agents for obesity or other MCH-mediated disorders.
Tan
Carina P
CP
Department of Obesity and Metabolic Research, Merck Research Laboratories, Rahway, NJ 07065, USA.
Sano
Hideki
H
Iwaasa
Hisashi
H
Pan
Jie
J
Sailer
Andreas W
AW
Hreniuk
Donna L
DL
Feighner
Scott D
SD
Palyha
Oksana C
OC
Pong
Sheng-Shung
SS
Figueroa
David J
DJ
Austin
Christopher P
CP
Jiang
Michael M
MM
Yu
Hong
H
Ito
Junko
J
Ito
Makoto
M
Ito
Masahiko
M
Guan
Xiao Ming
XM
MacNeil
Douglas J
DJ
Kanatani
Akio
A
Van der Ploeg
Lex H T
LH
Howard
Andrew D
AD
D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D008322:Mammals / Q000235:genetics*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone / Q000235:genetics*; D017481:Receptors, Somatostatin / Q000235:genetics*; D016415:Sequence Alignment; D013045:Species Specificity
C103263:MCHR1 protein, human; C491208:MCHR1 protein, rat; C431280:MCHR2 protein, human; C491209:Mchr1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone; D017481:Receptors, Somatostatin