Cnr2, encoding cannabinoid receptor type 2 (CB2R), is mainly expressed by leukocytes and has immunomodulatory functions. It is involved in the endogenous cannabinoid system (ECS) and can modulate immune responses through various pathways, playing a significant role in multiple biological processes [1,4]. Genetic models, such as KO mouse models, are valuable for studying its functions.

In KO mouse models, Cnr2 deficiency confers resistance to inflammation-induced preterm birth in mice, likely due to increased IL-10 production via augmented cAMP accumulation [4]. Mice missing Cnr1 and Cnr2 show implantation defects, with compromised blastocyst-uterine interactions and heightened edema around the implantation chamber, suggesting Cnr2's role in implantation [3]. Also, Cnr2-deficient larvae have severely perturbed sensory synapses in hair cells and photoreceptors, affecting sensory information processing [2]. Depression exacerbates myocardial ischemia-reperfusion injury in mice via down-regulation of Cnr2, which attenuates the MIF-AMPK signaling pathway activation [5].

In conclusion, Cnr2 is crucial for multiple biological processes including implantation, preterm birth prevention, sensory synapse function, and myocardial protection. The study of Cnr2 KO mouse models has revealed its role in these processes, providing insights into related disease mechanisms and potential therapeutic targets for implantation-related issues, preterm birth, sensory disorders, and myocardial ischemia-reperfusion injury.

References:

1. Grabon, Wanda, Bodennec, Jacques, Rheims, Sylvain, Belmeguenai, Amor, Bezin, Laurent. 2023. Update on the controversial identity of cells expressing cnr2 gene in the nervous system. In CNS neuroscience & therapeutics, 29, 760-770. doi:10.1111/cns.13977. https://pubmed.ncbi.nlm.nih.gov/36604187/

2. Colón-Cruz, Luis, Rodriguez-Morales, Roberto, Santana-Cruz, Alexis, Varshney, Gaurav K, Behra, Martine. 2021. Cnr2 Is Important for Ribbon Synapse Maturation and Function in Hair Cells and Photoreceptors. In Frontiers in molecular neuroscience, 14, 624265. doi:10.3389/fnmol.2021.624265. https://pubmed.ncbi.nlm.nih.gov/33958989/

3. Li, Yingju, Bian, Fenghua, Sun, Xiaofei, Dey, Sudhansu K. . Mice Missing Cnr1 and Cnr2 Show Implantation Defects. In Endocrinology, 160, 938-946. doi:10.1210/en.2019-00024. https://pubmed.ncbi.nlm.nih.gov/30776303/

4. Sun, Xiaofei, Cappelletti, Monica, Li, Yingju, Divanovic, Senad, Dey, Sudhansu K. 2014. Cnr2 deficiency confers resistance to inflammation-induced preterm birth in mice. In Endocrinology, 155, 4006-14. doi:10.1210/en.2014-1387. https://pubmed.ncbi.nlm.nih.gov/25051450/

5. Qian, Lu, Zhang, Suqin, Lin, Cong, Lin, Jiafeng, Li, Zhuoyuan. 2024. Depression exacerbates myocardial ischemia-reperfusion injury in mice via CNR2 gene and MIF-AMPK signaling pathway. In International journal of cardiology, 416, 132505. doi:10.1016/j.ijcard.2024.132505. https://pubmed.ncbi.nlm.nih.gov/39222886/