Genomes and Genes
Gene Symbol: Mc3r
Description: melanocortin 3 receptor
Alias: MC3-R, melanocortin receptor 3
- Butler A, Kesterson R, Khong K, Cullen M, Pelleymounter M, DeKoning J, et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology. 2000;141:3518-21 pubmed..To assess the role of the MC3-R in energy homeostasis, the majority of the mc3r coding sequence was deleted from the mouse genome...
- Ellacott K, Murphy J, Marks D, Cone R. Obesity-induced inflammation in white adipose tissue is attenuated by loss of melanocortin-3 receptor signaling. Endocrinology. 2007;148:6186-94 pubmed
- Chen A, Marsh D, Trumbauer M, Frazier E, Guan X, Yu H, et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet. 2000;26:97-102 pubmed..The physiological function of Mc3r, a melanocortin receptor expressed at high levels in the hypothalamus, has remained unknown...
- Sutton G, Trevaskis J, Hulver M, McMillan R, Markward N, Babin M, et al. Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors. Endocrinology. 2006;147:2183-96 pubmed..Little is known about how Mc3r or Mc4r genotype, diet, and obesity affect insulin sensitivity...
- Malas S, Peters J, Abbott C. The genes for endothelin 3, vitamin D 24-hydroxylase, and melanocortin 3 receptor map to distal mouse chromosome 2, in the region of conserved synteny with human chromosome 20. Mamm Genome. 1994;5:577-9 pubmed
- Chen H, Trumbauer M, Chen A, Weingarth D, Adams J, Frazier E, et al. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology. 2004;145:2607-12 pubmed..Here we describe treatment of Agrp(-/-);Npy(-/-) and Mc3r(-/-);Mc4r(-/-) double knockout mice as well as Npy(-/-) and Agrp(-/-) single knockout mice with either ghrelin or ..
- Rowland N, Schaub J, Robertson K, Andreasen A, Haskell Luevano C. Effect of MTII on food intake and brain c-Fos in melanocortin-3, melanocortin-4, and double MC3 and MC4 receptor knockout mice. Peptides. 2010;31:2314-7 pubmed publisherMice with genomic knockout of either melanocortin type 3 receptors (MC3R-/-), type 4 receptors (MC4R-/-) or knockout of both (double knockout, DKO) were tested for their anorectic response to the mixed MC3/4R agonist, MTII, injected into ..
- Augustine K, Rossi R. Rodent mutant models of obesity and their correlations to human obesity. Anat Rec. 1999;257:64-72 pubmed..In this review, we discuss the physiology and genetics underlying obesity and how studies in rodents and humans are converging, producing a greater understanding of the mechanisms underlying this health problem. ..
- Montero Melendez T, Madeira M, Norling L, Alsam A, Curtis M, da Silva T, et al. Association between periodontal disease and inflammatory arthritis reveals modulatory functions by melanocortin receptor type 3. Am J Pathol. 2014;184:2333-41 pubmed publisher..Further analyses in nonarthritic animals revealed higher susceptibility to periodontal bone loss in Mc3r(-/-) compared with wild-type mice, with significant exacerbation at 14 weeks of age...
- Zemel M. Agouti/melanocortin interactions with leptin pathways in obesity. Nutr Rev. 1998;56:271-4 pubmed..Both of these actions occur via a Ca(2+)-dependent mechanism, suggesting that modulation of adipocyte Ca2+ transport may be a key target for further investigation. ..
- Perez Tilve D, Hofmann S, Basford J, Nogueiras R, Pfluger P, Patterson J, et al. Melanocortin signaling in the CNS directly regulates circulating cholesterol. Nat Neurosci. 2010;13:877-82 pubmed publisher..Our data suggest that a neural circuit in the brain is directly involved in the control of cholesterol metabolism by the liver. ..
- Logan D, Bryson Richardson R, Pagán K, Taylor M, Currie P, Jackson I. The structure and evolution of the melanocortin and MCH receptors in fish and mammals. Genomics. 2003;81:184-91 pubmed..Zebrafish have six melanocortin receptors, including two MC5R orthologues, while Fugu, lacking MC3R, has only four. We also demonstrate that Fugu and zebrafish have two and three MCHR genes, respectively...
- Shindo M, Nakano H, Kuroyanagi H, Shirasawa T, Mihara M, Gilbert D, et al. cDNA cloning, expression, subcellular localization, and chromosomal assignment of mammalian aurora homologues, aurora-related kinase (ARK) 1 and 2. Biochem Biophys Res Commun. 1998;244:285-92 pubmed..Interspecific backcross mapping revealed that Ark1 is located in a distal region of mouse chromosome 2, while Ark2 is located in a central region of mouse chromosome 11. ..
- O Shaughnessy P, Fleming L, Jackson G, Hochgeschwender U, Reed P, Baker P. Adrenocorticotropic hormone directly stimulates testosterone production by the fetal and neonatal mouse testis. Endocrinology. 2003;144:3279-84 pubmed..Results show that both LH and ACTH can regulate testicular steroidogenesis during fetal development in the mouse and suggest that fetal Leydig cells, but not adult Leydig cells, are sensitive to ACTH stimulation. ..
- Patel H, Bombardieri M, Sampaio A, D Acquisto F, Gray M, Grieco P, et al. Anti-inflammatory and antiosteoclastogenesis properties of endogenous melanocortin receptor type 3 in experimental arthritis. FASEB J. 2010;24:4835-43 pubmed publisher..Overall, these findings identify MC(3)-mediated signaling as a beneficial pathway in experimental arthritis; hence this receptor is a novel target for the development of therapeutics for arthritis. ..
- Nogueiras R, Wiedmer P, Perez Tilve D, Veyrat Durebex C, Keogh J, Sutton G, et al. The central melanocortin system directly controls peripheral lipid metabolism. J Clin Invest. 2007;117:3475-88 pubmed..We also reveal molecular underpinnings for direct control of the CNS-Mcr over lipid metabolism. These results suggest ways to design more efficient pharmacological methods for controlling adiposity. ..
- Zhang Z, Felder R. Melanocortin receptors mediate the excitatory effects of blood-borne murine leptin on hypothalamic paraventricular neurons in rat. Am J Physiol Regul Integr Comp Physiol. 2004;286:R303-10 pubmed
- Renquist B, Murphy J, Larson E, Olsen D, Klein R, Ellacott K, et al. Melanocortin-3 receptor regulates the normal fasting response. Proc Natl Acad Sci U S A. 2012;109:E1489-98 pubmed publisher..Thus, MC3-R is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning, and this defect explains much of the metabolic phenotype in the model. ..
- Chagnon Y, Bouchard C. Genetics of obesity: advances from rodent studies. Trends Genet. 1996;12:441-4 pubmed
- Miner J, Patton B, Lentz S, Gilbert D, Snider W, Jenkins N, et al. The laminin alpha chains: expression, developmental transitions, and chromosomal locations of alpha1-5, identification of heterotrimeric laminins 8-11, and cloning of a novel alpha3 isoform. J Cell Biol. 1997;137:685-701 pubmed..Together, these results reveal remarkable diversity in BL composition and complexity in BL development. ..
- Montero Melendez T, Patel H, Seed M, Nielsen S, Jonassen T, Perretti M. The melanocortin agonist AP214 exerts anti-inflammatory and proresolving properties. Am J Pathol. 2011;179:259-69 pubmed publisher..These findings might clarify the tissue-protective properties of AP214 in clinical settings and may open further development for novel MC agonists. ..
- Okutsu K, Ojima F, Shinohara N, Taniuchi S, Mizote Y, Aoki K, et al. Functional characterization of the mouse melanocortin 3 receptor gene promoter. Gene. 2015;562:62-9 pubmed publisherb>Melanocortin receptor 3 (MC3R) is expressed in the hypothalamus and pituitary in humans and rodents, and is involved in the control of feeding, energy metabolism, and pituitary function...
- Ni X, Pearce D, Butler A, Cone R, Humphreys M. Genetic disruption of gamma-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse. J Clin Invest. 2003;111:1251-8 pubmed..targeted disruption of the PC2 gene (PC2(-/-)), necessary for processing of POMC into gamma-MSH, or the melanocortin receptor 3 gene (Mc3r(-/-); the receptor for MSH)...
- Irani B, Xiang Z, Yarandi H, Holder J, Moore M, Bauzo R, et al. Implication of the melanocortin-3 receptor in the regulation of food intake. Eur J Pharmacol. 2011;660:80-7 pubmed publisher..These data support the hypothesis that the MC(3) plays a subtle role in the regulation of food intake, however the mechanism by which this is occurring remains to be determined. ..
- Almodovar A, Luther R, Stonebrook C, Wood P. Genomic structure and genetic drift in C57BL/6 congenic metabolic mutant mice. Mol Genet Metab. 2013;110:396-400 pubmed publisher..mutant mouse lines to include the A) long-chain acyl-CoA dehydrogenase (Acadl), B) melanocortin 3 receptor (Mc3r), C) endothelial nitric oxide synthase (Nos3), and D) a replacement of mouse apolipoprotein E (Apoe) by human ..
- Taylor Douglas D, Basu A, Gardner R, Aspelund S, Wen X, Yanovski J. Evaluation of hypothalamic murine and human melanocortin 3 receptor transcript structure. Biochem Biophys Res Commun. 2014;454:234-8 pubmed publisherThe melanocortin 3 receptor (MC3R) is involved in regulation of energy homeostasis. However, its transcript structure is not well understood...
- Muceniece R, Zvejniece L, Liepinsh E, Kirjanova O, Baumane L, Petrovska R, et al. The MC3 receptor binding affinity of melanocortins correlates with the nitric oxide production inhibition in mice brain inflammation model. Peptides. 2006;27:1443-50 pubmed..90; p = 0.0008), whereas weak correlation was present for the other receptors. Our results suggest that the MC3 receptor is the major player in mediating the anti-inflammatory activity of MCs in the central nervous system. ..
- Wachira S, Guruswamy B, Uradu L, Hughes Darden C, Denaro F. Activation and endocytic internalization of melanocortin 3 receptor in neuronal cells. Ann N Y Acad Sci. 2007;1096:271-86 pubmed..Studies with gene knockout mice have implicated neural melanocortin receptors, MC3R and MC4R, in the etiology of obesity, insulin resistance, and salt-sensitive hypertension...
- Magenis R, Smith L, Nadeau J, Johnson K, Mountjoy K, Cone R. Mapping of the ACTH, MSH, and neural (MC3 and MC4) melanocortin receptors in the mouse and human. Mamm Genome. 1994;5:503-8 pubmed..The data reported here also show that the neural MC3 receptor maps close to a disease locus for benign neonatal epilepsy in human and near the E1-2 epilepsy susceptibility locus in the mouse. ..
- Garcia Tornadú I, Diaz Torga G, Risso G, Silveyra P, Cataldi N, Ramirez M, et al. Hypothalamic orexin, OX1, alphaMSH, NPY and MCRs expression in dopaminergic D2R knockout mice. Neuropeptides. 2009;43:267-74 pubmed publisher..No differences were found in hypothalamic NPY, MC3R or MC4R concentration...
- Ewart Toland A, Briassouli P, de Koning J, Mao J, Yuan J, Chan F, et al. Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human. Nat Genet. 2003;34:403-12 pubmed..This interaction results in colocalization of UBE2N with STK15 at the centrosomes during mitosis. These results are consistent with an important role for the Ile31 variant of STK15 in human cancer susceptibility. ..
- Fan W, Ellacott K, Halatchev I, Takahashi K, Yu P, Cone R. Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system. Nat Neurosci. 2004;7:335-6 pubmed
- Leoni G, Patel H, Sampaio A, Gavins F, Murray J, Grieco P, et al. Inflamed phenotype of the mesenteric microcirculation of melanocortin type 3 receptor-null mice after ischemia-reperfusion. FASEB J. 2008;22:4228-38 pubmed publisher..Here we addressed the pathophysiological effect that one MCR, MCR type 3 (MC3R), might have on vascular inflammation...
- Takeuchi S, Takahashi S. A possible involvement of melanocortin 3 receptor in the regulation of adrenal gland function in the chicken. Biochim Biophys Acta. 1999;1448:512-8 pubmed..Noteworthy, MC1-R gene was found to be a quite unique member of the chicken MC-R family with regard to GC content and codon usage. It may reflect as yet unidentified evolutionary pressure operating specifically on the gene. ..
- Marks D, Butler A, Turner R, Brookhart G, Cone R. Differential role of melanocortin receptor subtypes in cachexia. Endocrinology. 2003;144:1513-23 pubmed..These data underscore the importance of central melanocortin signaling in weight homeostasis and demonstrate differential effects of MC3-R and MC4-R blockade on the development of cachexia. ..
- Butler A, Cone R. Knockout studies defining different roles for melanocortin receptors in energy homeostasis. Ann N Y Acad Sci. 2003;994:240-5 pubmed..Two melanocortin receptors (MC3R, MC4R) are expressed in brain regions receiving projections of POMC fibers, most of which also receive projections ..
- Hiramoto K, Kobayashi H, Ishii M, Sato E, Inoue M. Increased alpha-melanocyte-stimulating hormone (alpha-MSH) levels and melanocortin receptors expression associated with pigmentation in an NC/Nga mouse model of atopic dermatitis. Exp Dermatol. 2010;19:132-6 pubmed publisher..the expression of melanocortin receptor 5 and melanocortin receptor 1 (MC1R) increased in the skin, and melanocortin receptor 3 (MC3R) expression increased in the intestine...
- Fan W, Boston B, Kesterson R, Hruby V, Cone R. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. 1997;385:165-8 pubmed..Our data show that melanocortinergic neurons exert a tonic inhibition of feeding behaviour. Chronic disruption of this inhibitory signal is a likely explanation of the agouti obesity syndrome. ..
- Butler A, Marks D, Fan W, Kuhn C, Bartolome M, Cone R. Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Nat Neurosci. 2001;4:605-11 pubmed..Leptin-deficient and MC3R-/- mice regulate metabolic rate similarly to wild-type mice in this protocol...
- Gantz I, Shimoto Y, Konda Y, Miwa H, Dickinson C, Yamada T. Molecular cloning, expression, and characterization of a fifth melanocortin receptor. Biochem Biophys Res Commun. 1994;200:1214-20 pubmed..Northern blot analysis demonstrated the expression of mMC5R mRNA in mouse skeletal muscle, lung, spleen, and brain. ..
- Williamson C, Dutton E, Abbott C, Beechey C, Ball S, Peters J. Thirteen genes (Cebpb, E2f1, Tcf4, Cyp24, Pck1, Acra4, Edn3, Kcnb1, Mc3r, Ntsr, Cd40, Plcg1 and Rcad) that probably lie in the distal imprinting region of mouse chromosome 2 are not monoallelically expressed. Genet Res. 1995;65:83-93 pubmed..express transcription factors, 2 genes (Cyp24 and Pck1) that are involved in growth, 5 genes (Acra4, Edn3, Kcnb1, Mc3r and Ntsr) where a defect could lead to neurological and probably behavioural problems, and 3 genes (Cd40, Plcg1 and ..
- Trevaskis J, Gawronska Kozak B, Sutton G, McNeil M, Stephens J, Smith S, et al. Role of adiponectin and inflammation in insulin resistance of Mc3r and Mc4r knockout mice. Obesity (Silver Spring). 2007;15:2664-72 pubmed..A delay in macrophage infiltration of adipose tissue of Mc3rKO during exposure to HFD may also be a factor contributing to the mild insulin resistance in this model. ..
- Lippert R, Ellacott K, Cone R. Gender-specific roles for the melanocortin-3 receptor in the regulation of the mesolimbic dopamine system in mice. Endocrinology. 2014;155:1718-27 pubmed publisherThe melanocortin-3 receptor (MC3R) and MC4R are known to play critical roles in energy homeostasis. However, the physiological functions of the MC3R remain poorly understood...
- Lute B, Jou W, Lateef D, Goldgof M, Xiao C, PiÃ±ol R, et al. Biphasic effect of melanocortin agonists on metabolic rate and body temperature. Cell Metab. 2014;20:333-45 pubmed publisher..is preceded by a profound, transient hypometabolism/hypothermia that is preserved in mice lacking any one of Mc1r, Mc3r, Mc4r, or Mc5r...
- Lee B, Koo J, Yun Jun J, Gavrilova O, Lee Y, Seo A, et al. A mouse model for a partially inactive obesity-associated human MC3R variant. Nat Commun. 2016;7:10522 pubmed publisherWe previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls...
- Arteaga Solis E, Zee T, Emala C, Vinson C, Wess J, Karsenty G. Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma. Cell Metab. 2013;17:35-48 pubmed publisher..These findings may be of use in the management of obesity-associated asthma. ..
- Rediger A, Piechowski C, Yi C, Tarnow P, Strotmann R, Gruters A, et al. Mutually opposite signal modulation by hypothalamic heterodimerization of ghrelin and melanocortin-3 receptors. J Biol Chem. 2011;286:39623-31 pubmed publisher..The ghrelin (growth hormone secretagogue receptor (GHSR)) and melanocortin-3 (MC3R) receptors are both known to have orexigenic effects on the hypothalamic control of body weight...
- Kumar K, Trevaskis J, Lam D, Sutton G, Koza R, Chouljenko V, et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008;8:468-81 pubmed publisher..Adropin may therefore be a factor governing glucose and lipid homeostasis, which protects against hepatosteatosis and hyperinsulinemia associated with obesity. ..
- De Miguel M, Centanni J, Gopalan G, Gilbert D, Copeland N, Jenkins N, et al. Cellular apoptosis susceptibility gene capts maps to mouse chromosome 2. Mamm Genome. 1998;9:411-2 pubmed
- Brommage R, Desai U, Revelli J, Donoviel D, Fontenot G, Dacosta C, et al. High-throughput screening of mouse knockout lines identifies true lean and obese phenotypes. Obesity (Silver Spring). 2008;16:2362-7 pubmed publisher..d. above the mean for four (MC4R, MC3R, BRS3, translin) but close to the mean for 5HT2cR...
- Mavrikaki M, Girardet C, Kern A, Faruzzi Brantley A, Miller C, Macarthur H, et al. Melanocortin-3 receptors in the limbic system mediate feeding-related motivational responses during weight loss. Mol Metab. 2016;5:566-579 pubmed publisher..The role of neural melanocortin-3 receptors (MC3R) in mediating these responses is enigmatic...
- Shaw A, Irani B, Moore M, Haskell Luevano C, Millard W. Ghrelin-induced food intake and growth hormone secretion are altered in melanocortin 3 and 4 receptor knockout mice. Peptides. 2005;26:1720-7 pubmed..of AGRP/melanocortin signaling in ghrelin-induced food intake by studying melanocortin 3 and 4 receptor knockout (MC3R KO and MC4R KO) mice...
- Desarnaud F, Labbe O, Eggerickx D, Vassart G, Parmentier M. Molecular cloning, functional expression and pharmacological characterization of a mouse melanocortin receptor gene. Biochem J. 1994;299 ( Pt 2):367-73 pubmed..The availability of functionally expressed receptors from the melanocortin family will allow the development of a specific pharmacology, and a better understanding of the function of the pro-opiomelanocortin-derived peptides. ..
- Begriche K, Marston O, Rossi J, Burke L, McDonald P, Heisler L, et al. Melanocortin-3 receptors are involved in adaptation to restricted feeding. Genes Brain Behav. 2012;11:291-302 pubmed publisher..Here, we characterized the response of Mc3r knockout (Mc3r(-/-)) and wild type (WT) mice to a restricted feeding (RF) schedule where food access was limited to ..
- Kiefer L, Veal J, Mountjoy K, Wilkison W. Melanocortin receptor binding determinants in the agouti protein. Biochemistry. 1998;37:991-7 pubmed..These agouti variants with altered receptor selectivity may be useful in determining the role of melanocortin receptors in diabetes and obesity. ..
- Atalayer D, Robertson K, Haskell Luevano C, Andreasen A, Rowland N. Food demand and meal size in mice with single or combined disruption of melanocortin type 3 and 4 receptors. Am J Physiol Regul Integr Comp Physiol. 2010;298:R1667-74 pubmed publisher..are known to be hyperphagic and become obese, while those with disruption of the melanocortin-3 receptor gene (MC3R-/-) do not become markedly obese. The contribution of MC3R signaling in energy homeostasis remains little studied...
- Girardet C, Mavrikaki M, Southern M, Smith R, Butler A. Assessing interactions between Ghsr and Mc3r reveals a role for AgRP in the expression of food anticipatory activity in male mice. Endocrinology. 2014;155:4843-55 pubmed publisher..the interaction between Ghsrs and Mc3rs, we compared food anticipatory responses in GhsrKO, Mc3rKO, and double Ghsr;Mc3r knockout (DKO) mice subjected to a hypocaloric restricted feeding (RF) protocol in constant dark or 12-hour light, ..
- Ni X, Butler A, Cone R, Humphreys M. Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones. J Hypertens. 2006;24:2239-46 pubmed..injections of synthetic alpha or gamma-MSH intravenously or intracerebroventricularly to anesthetized wild-type (Mc3r+/+, Mc4r+/+) mice and mice with targeted disruption of the gamma-MSH receptor (Mc3r-/-) or the melanocortin 4 ..
- Schioth H, Muceniece R, Szardenings M, Prusis P, Wikberg J. Evidence indicating that the TM4, EL2, and TM5 of the melanocortin 3 receptor Do not participate in ligand binding. Biochem Biophys Res Commun. 1996;229:687-92 pubmed..The data provide further evidence, that the mutated regions may not participate at all in ligand binding, as indicated by modelling experiments and homology comparison. ..