Muc13-KO Mouse

MUC13, a transmembrane glycoprotein, is highly expressed on the mucosal surface throughout the intestine. It participates in multiple biological processes, such as protecting the mucosal epithelial barrier, and is involved in pathways like Wnt/β-catenin, ERK, and EGFR/PI3K/AKT. MUC13 is of great biological importance as it is associated with cancer progression and antimicrobial defense [1-2].

In Muc13 -/- mice, fewer tumors are generated after exposure to carcinogens and inflammation, with reduced β-catenin signaling, more tumor-infiltrating CD103+ dendritic cells and CD8+ T lymphocytes, and fewer myeloid-derived suppressor cells. These mice also become sensitive to checkpoint inhibitor immunotherapy (anti-PD-L1), indicating MUC13's role in promoting colitis-associated colorectal tumor development via β-catenin activity [2]. In another study, S. Typhimurium-infected Muc13 -/- mice had increased disease activity, histologic damage, and higher local and systemic bacterial loads, revealing MUC13's critical role in antimicrobial defense against pathogenic S. Typhimurium at the intestinal mucosal surface [1].

In conclusion, MUC13 plays essential roles in protecting the intestinal mucosal barrier from bacterial infection and promoting the development of certain cancers, especially colorectal cancer. The use of Muc13 KO mouse models has significantly contributed to understanding its functions in these disease-related processes, providing potential therapeutic targets for cancer treatment and insights into mucosal defense mechanisms.

References:

1. McGuckin, Michael A, Davies, Julie M, Felgner, Pascal, Hensel, Michael, Sheng, Yong H. 2023. MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier. In Cellular and molecular gastroenterology and hepatology, 16, 985-1009. doi:10.1016/j.jcmgh.2023.08.011. https://pubmed.ncbi.nlm.nih.gov/37660948/

2. Sheng, Yong Hua, Wong, Kuan Yau, Seim, Inge, Hasnain, Sumaira, McGuckin, Michael A. 2019. MUC13 promotes the development of colitis-associated colorectal tumors via β-catenin activity. In Oncogene, 38, 7294-7310. doi:10.1038/s41388-019-0951-y. https://pubmed.ncbi.nlm.nih.gov/31427737/