Vipr2, also known as VPAC2, is a receptor that binds vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) with high affinity. It is involved in multiple physiological processes. In the brain, it has a pivotal role in regulating circadian rhythms and impacts processes related to fear cognition. It is also part of signaling pathways, such as the cAMP signaling pathway [1].

Gene knockout studies have provided significant insights. In Vipr2 knockout (Vipr2-KO) mice, refraction was shifted towards myopia, suggesting that Vipr2 dysfunction may lead to myopia. The amplitudes of bipolar cell-derived b-waves were larger in these KO mice, indicating a potential compromise in bipolar cell function due to altered signal transduction [2]. In mice overexpressing Vipr2, there was 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. This implies that overactive Vipr2 signaling during development may play a role in some forms of schizophrenia [3].

In conclusion, Vipr2 is crucial for normal physiological functions, especially in the regulation of the eye's refractive state and in brain development. Vipr2-KO and overexpression mouse models have been instrumental in uncovering its role in myopia and schizophrenia, respectively. These models provide a foundation for understanding the underlying mechanisms of these diseases and may potentially guide the development of novel therapeutic strategies.

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/