Mc3r-KO Mouse

Mc3r, the melanocortin 3 receptor, is a G-protein coupled receptor. It is mainly known as a regulator of the appetite/hunger balance mechanisms. It is also involved in the central melanocortin system, which is crucial for energy homeostasis [1]. Genetic models, such as gene knockout (KO) mouse models, have been instrumental in studying its functions.

Mice lacking Mc3r have shown delayed sexual maturation, insensitivity of reproductive cycle length to nutritional perturbation, reduced linear growth, lean mass, and circulating levels of IGF1 [2]. In humans, carriers of loss-of-function mutations in MC3R also have a later onset of puberty. Functionally damaging variants in MC3R are overrepresented in individuals with constitutional delay of growth and puberty (CDGP) [3]. Inhibition of MC3R in mice improves the dose-responsiveness to anorexigenic agents like Glucagon-like peptide 1 (GLP1) agonists [4].

In conclusion, Mc3r plays essential roles in regulating sexual maturation, linear growth, lean mass accrual, and appetite. KO mouse models have been key in revealing its role in CDGP. These findings enhance our understanding of the biological processes regulated by Mc3r and its potential implications in related disease conditions.

References:

1. Yanik, Tulin, Durhan, Seyda Tugce. 2022. Specific Functions of Melanocortin 3 Receptor (MC3R). In Journal of clinical research in pediatric endocrinology, 15, 1-6. doi:10.4274/jcrpe.galenos.2022.2022-5-21. https://pubmed.ncbi.nlm.nih.gov/36053086/

2. Lam, B Y H, Williamson, A, Finer, S, Yeo, G S, O'Rahilly, S. 2021. MC3R links nutritional state to childhood growth and the timing of puberty. In Nature, 599, 436-441. doi:10.1038/s41586-021-04088-9. https://pubmed.ncbi.nlm.nih.gov/34732894/

3. Duckett, Katie, Williamson, Alice, Kincaid, John W R, Ong, Ken K, O'Rahilly, Stephen. . Prevalence of Deleterious Variants in MC3R in Patients With Constitutional Delay of Growth and Puberty. In The Journal of clinical endocrinology and metabolism, 108, e1580-e1587. doi:10.1210/clinem/dgad373. https://pubmed.ncbi.nlm.nih.gov/37339320/

4. Dahir, Naima S, Gui, Yijun, Wu, Yanan, Mapp, Anna K, Cone, Roger D. 2023. Inhibition of the melanocortin-3 receptor (MC3R) causes generalized sensitization to anorectic agents. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.12.05.570114. https://pubmed.ncbi.nlm.nih.gov/38106197/