Prok2, also known as prokineticin 2, is an important secreted protein. It functions through the activation of two G-protein receptors (PROKR1 and PROKR2) and is involved in multiple biological functions, such as regulating gastrointestinal motility, circadian rhythm, neurogenesis, angiogenesis, pain perception, and mood regulation [1]. The Prok2-PROKR2 signaling pathway is also associated with various biological processes like the migration of olfactory bulb interneurons and is likely involved in the pathogenesis of some neurological diseases [2,3]. Genetic models, especially KO/CKO mouse models, can be valuable in studying Prok2.

In Prok2 and Prokr2 mutant mice, there are severe tangential and radial migration defects of neuroblasts in the subventricular zone-rostral migratory stream-olfactory bulb (SVZ-RMS-OB), resulting in the loss of about 75% of GABAergic interneurons in the OB, demonstrating that PROK2/PROKR2 signaling is crucial for the migration of OB interneurons [2]. In a model of traumatic brain injury, mice injected with adeno-associated virus-Prok2 before injury showed reduced neuronal degeneration and improved motor and cognitive functions, suggesting Prok2 mediates neuronal cell deaths in traumatic brain injury via ferroptosis [3].

In conclusion, Prok2 is essential for multiple biological functions, including neuronal migration and protection against neuronal cell death in traumatic brain injury. Studies using KO/CKO mouse models have been instrumental in revealing these functions, contributing to our understanding of related biological processes and disease mechanisms [2,3].

References:

1. Petrella, Carla, Spaziani, Matteo, D'Orazi, Valerio, Ferraguti, Giampiero, Fiore, Marco. 2022. Prokineticin 2/PROK2 and Male Infertility. In Biomedicines, 10, . doi:10.3390/biomedicines10102389. https://pubmed.ncbi.nlm.nih.gov/36289651/

2. Wen, Yan, Zhang, Zhuangzhi, Li, Zhenmeiyu, Li, Jiada, Yang, Zhengang. 2019. The PROK2/PROKR2 signaling pathway is required for the migration of most olfactory bulb interneurons. In The Journal of comparative neurology, 527, 2931-2947. doi:10.1002/cne.24719. https://pubmed.ncbi.nlm.nih.gov/31132148/

3. Bao, Zhongyuan, Liu, Yinlong, Chen, Binglin, Bayır, Hülya, Ji, Jing. 2021. Prokineticin-2 prevents neuronal cell deaths in a model of traumatic brain injury. In Nature communications, 12, 4220. doi:10.1038/s41467-021-24469-y. https://pubmed.ncbi.nlm.nih.gov/34244497/