Mc2r-KO Mouse

The melanocortin 2 receptor (MC2R), also known as the adrenocorticotropic hormone receptor (ACTHR), is a member of the G protein-coupled receptor family. It is selectively activated by adrenocorticotropic hormone (ACTH) and plays a crucial role in the hypothalamic-pituitary-adrenal (HPA) axis [1,2,3,4,5]. In this axis, it mediates responses to ACTH, which is vital for regulating glucocorticoid production, and thus is important for physiological stress responses, metabolism, and immune function [3].

Mutations in the MC2R gene can lead to type 1 familial glucocorticoid deficiency (FGD), an autosomal recessive disorder. For example, a novel homozygous missense mutation c.326T>A, p.Leu109Gln in the MC2R gene was found to disrupt cAMP production and MC2R protein expression, leading to ACTH resistance and FGD phenotypes [2]. Also, a homozygotic variant of c.712C>T/p.H238Y in MC2R was reported in a Chinese family with affected siblings showing features like skin hyperpigmentation, hyperbilirubinemia, tall stature, and congenital heart defects, expanding the genetic and clinical spectrum of FGD1 [4].

In conclusion, MC2R is essential for the proper functioning of the HPA axis and regulation of glucocorticoid synthesis. Studies on genetic mutations in MC2R, such as those causing FGD, have enhanced our understanding of the role of MC2R in maintaining normal physiological function and the pathophysiology of related diseases.