Elmo1-KO Mouse

Engulfment and cell motility protein 1 (ELMO1) is a key protein in innate immunity. It is essential for the clearance of apoptotic cells and pathogenic bacteria and for controlling inflammatory responses. ELMO1 binds with Dock180 to activate the Rac1 signaling pathway, playing a significant role in cellular shaping and motility, which is crucial for processes like bacterial phagocytosis, cancer cell invasion, and metastasis [1].

In various in vivo studies using gene knockout mouse models, ELMO1 has been shown to have diverse functions. In Elmo1 -/- mice, peritoneal inflammation was alleviated as neutrophil chemotaxis and adhesion were defective, suggesting ELMO1 is an important regulator of neutrophil activation during peritonitis [4]. In osteoporosis and arthritis models, ELMO1 deletion in mice reduced bone loss, and in a rheumatoid arthritis mouse model, bone erosion was alleviated in Elmo1 -/- mice, indicating its role in osteoclast function and bone resorption [6,7]. In ankylosing spondylitis, TNF-α-mediated m6A modification of ELMO1 in mesenchymal stem cells enhanced their directional migration, and inhibiting ELMO1 in SKG mice had therapeutic effects [2]. ELMO1 -/- platelets showed enhanced function, suggesting its role in hemostasis and thrombosis [3]. In intestinal fibrosis related to inflammatory bowel disease, deletion of ELMO1 led to senescent intestinal epithelial cell accumulation and premature fibrosis [5]. In primary biliary cholangitis, knockdown of ELMO1 in macrophages inhibited their migration and inflammatory factor secretion [8].

In conclusion, ELMO1 plays essential roles in multiple biological processes, especially in inflammation, cell motility, and bone metabolism. Gene knockout mouse models have been instrumental in revealing its functions in diseases such as peritonitis, osteoporosis, arthritis, ankylosing spondylitis, thrombotic diseases, intestinal fibrosis, and primary biliary cholangitis. These findings provide potential insights for developing new therapeutic strategies targeting ELMO1 in these disease areas.

References:

1. Tocci, Stefania, Ibeawuchi, Stella-Rita, Das, Soumita, Sayed, Ibrahim M. 2022. Role of ELMO1 in inflammation and cancer-clinical implications. In Cellular oncology (Dordrecht, Netherlands), 45, 505-525. doi:10.1007/s13402-022-00680-x. https://pubmed.ncbi.nlm.nih.gov/35668246/

2. Xie, Zhongyu, Yu, Wenhui, Zheng, Guan, Wu, Yanfeng, Shen, Huiyong. 2021. TNF-α-mediated m6A modification of ELMO1 triggers directional migration of mesenchymal stem cell in ankylosing spondylitis. In Nature communications, 12, 5373. doi:10.1038/s41467-021-25710-4. https://pubmed.ncbi.nlm.nih.gov/34508078/

3. Patel, Akruti, Kostyak, John, Dangelmaier, Carol, Goldfinger, Lawrence, Kunapuli, Satya. . ELMO1 deficiency enhances platelet function. In Blood advances, 3, 575-587. doi:10.1182/bloodadvances.2018016444. https://pubmed.ncbi.nlm.nih.gov/30787021/

4. Yu, Shuxiang, Geng, Xiaoke, Liu, Huibing, Li, Baojie, Yan, Jianshe. 2023. ELMO1 Deficiency Reduces Neutrophil Chemotaxis in Murine Peritonitis. In International journal of molecular sciences, 24, . doi:10.3390/ijms24098103. https://pubmed.ncbi.nlm.nih.gov/37175809/

5. Chen, Junguo, Li, Guanman, He, Xiaowen, Lian, Lei, He, Xiaosheng. 2024. ELMO1 ameliorates intestinal epithelial cellular senescence via SIRT1/p65 signaling in inflammatory bowel disease-related fibrosis. In Gastroenterology report, 12, goae045. doi:10.1093/gastro/goae045. https://pubmed.ncbi.nlm.nih.gov/38756351/

6. Arandjelovic, Sanja, Perry, Justin S A, Zhou, Ming, Conrads, Thomas P, Ravichandran, Kodi S. 2021. ELMO1 signaling is a promoter of osteoclast function and bone loss. In Nature communications, 12, 4974. doi:10.1038/s41467-021-25239-6. https://pubmed.ncbi.nlm.nih.gov/34404802/

7. Liang, Xinyue, Hou, Yafei, Han, Lijuan, Cao, Xiumei, Yan, Jianshe. 2021. ELMO1 Regulates RANKL-Stimulated Differentiation and Bone Resorption of Osteoclasts. In Frontiers in cell and developmental biology, 9, 702916. doi:10.3389/fcell.2021.702916. https://pubmed.ncbi.nlm.nih.gov/34381782/

8. Ma, Di, Liu, Xiaoxiao, Li, Jinyu, Ma, Jiaxuan, Tai, Wenlin. 2024. ELMO1 regulates macrophage directed migration and attenuates inflammation via NF-κB signaling pathway in primary biliary cholangitis. In Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 56, 1897-1905. doi:10.1016/j.dld.2024.05.012. https://pubmed.ncbi.nlm.nih.gov/38825413/