Vipr2, also known as the receptor for vasoactive intestinal peptide 2 (VPAC2), binds vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) with high affinity. It is involved in regulating various physiological processes such as circadian rhythms, fear cognition, and is part of signaling pathways like cAMP and phosphoinositide metabolism [1]. VIP-Vipr2 signaling can regulate cell migration, and its role in neural development and plasticity is also crucial, making it biologically significant. Genetic models, especially mouse models, are valuable for studying its functions.

In gene-knockout studies, Vipr2-knockout (Vipr2-KO) mice showed a significant shift in refraction towards myopia, suggesting that the loss of Vipr2 function may compromise bipolar cell function in the retina and is related to form-deprivation myopia development [2]. Overexpression of Vipr2 in mice led to microencephaly, with a reduction in brain weight, a decrease in hippocampus grey matter volume, and an increase in whole-brain white matter volume, along with sex-specific behavioral changes like impaired prepulse inhibition and contextual fear memory, indicating its role in brain morphogenesis and potentially in schizophrenia [3].

In conclusion, Vipr2 is essential in regulating physiological processes such as circadian rhythms, neural development, and cell migration. Model-based research, especially using Vipr2 KO mouse models, has revealed its role in myopia and potentially in schizophrenia. Understanding Vipr2 function provides insights into the mechanisms of these diseases, offering potential targets for treatment and prevention.

References:

1. Ago, Yukio, Asano, Satoshi, Hashimoto, Hitoshi, Waschek, James A. 2021. Probing the VIPR2 Microduplication Linkage to Schizophrenia in Animal and Cellular Models. In Frontiers in neuroscience, 15, 717490. doi:10.3389/fnins.2021.717490. https://pubmed.ncbi.nlm.nih.gov/34366784/

2. Zhao, Fuxin, Li, Qihang, Chen, Wei, Qu, Jia, Zhou, Xiangtian. 2020. Dysfunction of VIPR2 leads to myopia in humans and mice. In Journal of medical genetics, 59, 88-100. doi:10.1136/jmedgenet-2020-107220. https://pubmed.ncbi.nlm.nih.gov/33318135/

3. Ago, Yukio, Van, Christina, Condro, Michael C, MacKenzie-Graham, Allan J, Waschek, James A. 2023. Overexpression of VIPR2 in mice results in microencephaly with paradoxical increased white matter volume. In Experimental neurology, 362, 114339. doi:10.1016/j.expneurol.2023.114339. https://pubmed.ncbi.nlm.nih.gov/36717013/