Or2j3-KO Mouse

Or2j3, an olfactory receptor gene, is involved in smell perception and has functions beyond the olfactory epithelium. It plays a role in various signaling pathways, and its expression has been detected in multiple tissues and cell types. Olfactory receptors are key in sensing odors, and Or2j3's function in this regard might have implications for understanding the genetic basis of odor detection [2,3].

Stimulation of Or2j3 with cinnamaldehyde in lung epithelial cells reduces interleukin-8 (IL-8) secretion, cell proliferation, and wound healing, while increasing cAMP levels. This indicates its potential as a drug target for non-type 2 inflammation in lung diseases [1]. In a human pancreatic enterochromaffin cell line, the Or2j3-specific agonist helional induces a transient decrease in intracellular Ca2+ levels and a dose-dependent release of serotonin [4]. In non-small-cell lung cancer cells, helional-induced activation of Or2j3 promotes apoptosis, inhibits cell proliferation and migration [5]. Also, the gene expression of Or2j3 is downregulated in the frontal cortex of Parkinson's disease patients [6].

In summary, Or2j3 has diverse functions in different biological processes and disease conditions. Its role in lung diseases, pancreatic cell regulation, non-small-cell lung cancer, and Parkinson's disease highlights its importance. The findings from these studies using different cell models provide insights into the potential of Or2j3 as a therapeutic target in these disease areas.

References:

1. Weidinger, Daniel, Jacobsen, Julian, Alisch, Desiree, Hatt, Hanns, Knobloch, Jürgen. 2024. Olfactory receptors impact pathophysiological processes of lung diseases in bronchial epithelial cells. In European journal of cell biology, 103, 151408. doi:10.1016/j.ejcb.2024.151408. https://pubmed.ncbi.nlm.nih.gov/38583306/

2. McRae, Jeremy F, Mainland, Joel D, Jaeger, Sara R, Matsunami, Hiroaki, Newcomb, Richard D. 2012. Genetic variation in the odorant receptor OR2J3 is associated with the ability to detect the "grassy" smelling odor, cis-3-hexen-1-ol. In Chemical senses, 37, 585-93. doi:10.1093/chemse/bjs049. https://pubmed.ncbi.nlm.nih.gov/22714804/

3. Li, Bingjie, Kamarck, Marissa L, Peng, Qianqian, Mainland, Joel D, Wang, Sijia. 2022. From musk to body odor: Decoding olfaction through genetic variation. In PLoS genetics, 18, e1009564. doi:10.1371/journal.pgen.1009564. https://pubmed.ncbi.nlm.nih.gov/35113854/

4. Kalbe, Benjamin, Schlimm, Marian, Mohrhardt, Julia, Hatt, Hanns, Osterloh, Sabrina. 2016. Helional induces Ca2+ decrease and serotonin secretion of QGP-1 cells via a PKG-mediated pathway. In Journal of molecular endocrinology, 57, 201-10. doi:10.1530/JME-16-0063. https://pubmed.ncbi.nlm.nih.gov/27553203/

5. Kalbe, Benjamin, Schulz, Viola Maria, Schlimm, Marian, Osterloh, Sabrina, Hatt, Hanns. 2016. Helional-induced activation of human olfactory receptor 2J3 promotes apoptosis and inhibits proliferation in a non-small-cell lung cancer cell line. In European journal of cell biology, 96, 34-46. doi:10.1016/j.ejcb.2016.11.004. https://pubmed.ncbi.nlm.nih.gov/27939274/

6. Garcia-Esparcia, Paula, Schlüter, Agatha, Carmona, Margarita, Pujol, Aurora, Ferrer, Isidre. . Functional genomics reveals dysregulation of cortical olfactory receptors in Parkinson disease: novel putative chemoreceptors in the human brain. In Journal of neuropathology and experimental neurology, 72, 524-39. doi:10.1097/NEN.0b013e318294fd76. https://pubmed.ncbi.nlm.nih.gov/23656994/