Mrap2-KO Mouse

MRAP2, the melanocortin receptor-associated protein 2, is crucial for regulating energy homeostasis. It is involved in multiple pathways related to appetite control and body weight regulation, interacting with several G-protein-coupled receptors (GPCRs) such as the melanocortin-4 receptor (MC4R), ghrelin receptor (GHSR1a), and prokineticin receptors (PKR1 and PKR2) [1,2,3,4]. Genetic models, like MRAP2 knockout mice, have been valuable in understanding its functions.

In MRAP2 knockout mice, the orexigenic effect of ghrelin is lost, and fasting fails to activate agouti-related protein neurons, indicating MRAP2's role in hunger sensing and energy homeostasis regulation through modulation of ghrelin-GHSR1a signaling [3]. Also, MRAP2 knockout mice display an obese phenotype, similar to MC3R and MC4R knockout mice, suggesting its importance in controlling appetite and energy balance [5]. In addition, human mutations in MRAP2 are associated with monogenic hyperphagic obesity with hyperglycaemia and hypertension [5].

In conclusion, MRAP2 is a key regulator in energy homeostasis, playing a significant role in appetite control, hunger sensing, and body weight regulation. The study of MRAP2 knockout mouse models has provided insights into its functions in the context of obesity and related metabolic disorders, highlighting its potential as a therapeutic target for treating obesity and associated metabolic diseases.