Prok2-flox Mouse

Prok2, short for prokineticin 2, is a protein-coding gene. The prokineticin system, consisting of Prok2 and prokineticin 1 (PROK1), regulates a wide range of biological functions through activating two G-protein receptors (PROKR1 and PROKR2), such as gastrointestinal motility, circadian rhythm regulation, neurogenesis, angiogenesis, pain perception, and mood regulation [1].

In gene-knockout mouse models, the absence of Prok2 or its receptor PROKR2 leads to significant biological changes. In the context of olfactory bulb interneurons, Prok2-PROKR2 signaling is crucial. 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 a loss of about 75% of GABAergic interneurons in the olfactory bulb, indicating its importance in neuronal migration [3]. In the study of pleasant touch sensation, genetic ablation of Prok2 in sensory neurons abolishes the pleasant touch-conditioned place preference (PT-CPP) in mice without impairing pain and itch behaviors, suggesting Prok2 encodes and transmits pleasant touch to spinal PROKR2 neurons [2]. In spinal cord injury (SCI) rat models, up-regulation of Prok2 by injecting recombinant human Prok2 protein inhibits ferroptosis and reduces neurodegeneration, and this effect is mediated by PKR1 and PKR2 as silencing these receptors reverses the inhibition of ferroptosis, revealing the antiferroptotic and neuroprotective roles of Prok2/PKR signaling in SCI [6].

In conclusion, Prok2 is involved in multiple biological processes, such as neuronal migration, pleasant touch sensation, and ferroptosis regulation. Studies using gene-knockout models have significantly advanced our understanding of Prok2's role in these processes. In diseases like male infertility, cervical cancer, and neurological injuries (traumatic brain injury, spinal cord injury), Prok2 has emerged as a potential target, highlighting its importance in disease-related research and potential therapeutic development [1,4,5,6].