Olfm4-KO Mouse

Olfm4, or olfactomedin 4, is a gene with diverse functions. It is involved in multiple biological processes such as inflammation regulation, cell function modulation, and tumor-related activities. It has been associated with pathways like NF-κB, Wnt, and Hippo, which are crucial for maintaining normal physiological states and are often dysregulated in diseases [1,2,4]. Genetic models, especially KO/CKO mouse models, have been instrumental in understanding its function.

In KO mouse models, OLFM4-deficient mice showed several phenotypes. In sepsis-associated ARDS, OLFM4 may regulate the pro-inflammatory response of lung epithelial cells through LDHA-mediated NF-κB signaling, as its overexpression suppressed LPS-induced pro-inflammatory responses [1]. In intestinal inflammation, OLFM4-deficient mice were more susceptible to bacterial infection but more resistant to anti-CD40 induced innate colitis, with impaired IL-22 production by ILC3, indicating its role in modulating intestinal inflammation [3]. OLFM4-deficient mice lacking OLFM4 in myeloid cells had poor recruitment of PMN-MDSCs, impaired intestinal homeostasis, and delayed development from IBD to CRC [5]. Also, juvenile OLFM4-null mice had increased survival when sepsis was induced, with reduced renal cell apoptosis and plasma creatinine [6].

In conclusion, Olfm4 is a key gene involved in inflammation, cell function regulation, and disease progression. KO/CKO mouse models have revealed its role in diseases such as sepsis-associated ARDS, intestinal inflammation, and the progression from colitis to colorectal cancer. Understanding Olfm4 provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Gong, Fangchen, Li, Ranran, Zheng, Xiangtao, Mao, Enqiang, Chen, Erzhen. 2021. OLFM4 Regulates Lung Epithelial Cell Function in Sepsis-Associated ARDS/ALI via LDHA-Mediated NF-κB Signaling. In Journal of inflammation research, 14, 7035-7051. doi:10.2147/JIR.S335915. https://pubmed.ncbi.nlm.nih.gov/34955649/

2. Wei, Hongfa, Li, Wenchao, Zeng, Leli, Li, Jia, Zhang, Changhua. 2024. OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway. In Molecular cancer, 23, 124. doi:10.1186/s12943-024-02016-9. https://pubmed.ncbi.nlm.nih.gov/38849840/

3. Xing, Zhe, Li, Xinyao, He, Junyu, Guo, Yuxiong, He, Yumei. 2024. OLFM4 modulates intestinal inflammation by promoting IL-22+ILC3 in the gut. In Communications biology, 7, 914. doi:10.1038/s42003-024-06601-y. https://pubmed.ncbi.nlm.nih.gov/39075283/

4. Wen, Fuping, Han, Yi, Zhang, Hui, Zhou, Zhaocai, Jiao, Shi. 2024. Epstein-Barr virus infection upregulates extracellular OLFM4 to activate YAP signaling during gastric cancer progression. In Nature communications, 15, 10543. doi:10.1038/s41467-024-54850-6. https://pubmed.ncbi.nlm.nih.gov/39627192/

5. Chen, Ziyang, Zhang, Xiaogang, Xing, Zhe, Tao, Yingxu, He, Yumei. 2022. OLFM4 deficiency delays the progression of colitis to colorectal cancer by abrogating PMN-MDSCs recruitment. In Oncogene, 41, 3131-3150. doi:10.1038/s41388-022-02324-8. https://pubmed.ncbi.nlm.nih.gov/35487976/

6. Stark, Julie E, Opoka, Amy M, Mallela, Jaya, Wong, Hector R, Alder, Matthew N. 2020. Juvenile OLFM4-null mice are protected from sepsis. In American journal of physiology. Renal physiology, 318, F809-F816. doi:10.1152/ajprenal.00443.2019. https://pubmed.ncbi.nlm.nih.gov/32068457/