MTNR1B, encoding melatonin receptor 1B, is a key gene in the melatonergic system. Melatonin, a neurohormone involved in circadian rhythms, binds to MTNR1B, and this interaction may regulate various physiological processes [3,4]. Genetic variations in MTNR1B have been linked to multiple diseases, highlighting its importance in human health. Mouse models are valuable for studying MTNR1B's function in vivo.

In a Mtnr1b knockout mouse model, the deletion of Mtnr1b disrupted placental angiogenesis through the VEGF signaling pathway, leading to fetal growth restriction. Specifically, Mtnr1b knockout reduced the phosphorylation of STAT3, which downregulated VEGFR2 and its downstream elements of PI3K and AKT expressions, jeopardizing angiogenesis and placental development [1]. Astrocyte-specific knockout of Mtnr1b in mice (Mtnr1b cKO𝐺𝑓𝑎𝑝 mice) resulted in anxiety-like behavior. This was caused by the down-regulation of gamma-aminobutyric acid-ergic (GABAergic) synaptic function, as evidenced by decreased levels of GABAA receptors and Kir2.2 [2].

In conclusion, MTNR1B plays essential roles in placental function and neuronal behavior. Mtnr1b knockout and conditional knockout mouse models have revealed its significance in regulating placental angiogenesis and GABAergic synaptic function, contributing to our understanding of fetal growth restriction and anxiety-related disorders [1,2].

References:

1. Wang, Likai, Han, Qi, Yan, Laiqing, Zhang, Ran, Liu, Guoshi. 2024. Mtnr1b deletion disrupts placental angiogenesis through the VEGF signaling pathway leading to fetal growth restriction. In Pharmacological research, 206, 107290. doi:10.1016/j.phrs.2024.107290. https://pubmed.ncbi.nlm.nih.gov/38960012/

2. Meng, Zijun, Guo, Shipeng, Dong, Xiangjun, Zhou, Weihui, Song, Weihong. . Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male Mice. In Journal of integrative neuroscience, 22, 154. doi:10.31083/j.jin2206154. https://pubmed.ncbi.nlm.nih.gov/38176947/

3. Garaulet, Marta, Qian, Jingyi, Florez, Jose C, Saxena, Richa, Scheer, Frank A J L. 2020. Melatonin Effects on Glucose Metabolism: Time To Unlock the Controversy. In Trends in endocrinology and metabolism: TEM, 31, 192-204. doi:10.1016/j.tem.2019.11.011. https://pubmed.ncbi.nlm.nih.gov/31901302/

4. Bonnefond, Amélie, Froguel, Philippe. 2017. Disentangling the Role of Melatonin and its Receptor MTNR1B in Type 2 Diabetes: Still a Long Way to Go? In Current diabetes reports, 17, 122. doi:10.1007/s11892-017-0957-1. https://pubmed.ncbi.nlm.nih.gov/29063374/