Msn-KO Mouse

Msn, short for Moesin, is a member of the ezrin-radixin-moesin family. It connects the cell membrane to the actin-based cytoskeleton, regulating cell morphology. It is involved in multiple biological processes and is associated with pathways such as the β-catenin-RUNX2 axis and PKC-mediated CREB signaling pathway, playing important roles in cell proliferation, adhesion, migration, and invasion [1,2,3].

In patients, novel mutations in the Msn gene can lead to immunodeficiency. A 10-year-old boy with a novel hemizygous mutation (c.68 A > G, p.N23S) presented with recurrent fever, oral ulcers, dermatomyositis-like symptoms, EBV infection, and later developed nasal-type NK/T-cell lymphoma. His immunological phenotype included persistent decreases in T and B lymphocyte counts [1]. Two brothers with a hemizygous missense mutation (c.511C > T:p.R171W) had repeated lung infections, significantly decreased lymphocyte and neutrophil levels, and bronchiectasis and emphysema [4]. In cancer research, higher Msn expression in CRC tissues is associated with poor patient survival rates. Msn silencing inhibits CRC cell proliferation, adhesion, migration, and invasion in vitro, while overexpression accelerates these processes via the β-catenin-RUNX2 axis [2]. In TNBC, Msn is significantly overexpressed and promotes cell proliferation, invasion, and tumor growth through phosphorylation-mediated nuclear localization and activation of the CREB signaling pathway [3].

In conclusion, Msn is crucial in regulating cell-cytoskeleton interactions and associated biological functions. Studies on Msn gene-mutated patients have revealed its significance in immunodeficiency-related diseases. In cancer, Msn's role in promoting disease progression through specific signaling pathways makes it a potential therapeutic target for CRC and TNBC.

References:

1. Sun, Bijun, Liu, Luyao, Han, Lingli, Wang, Xiaochuan, Sun, Jinqiao. 2024. Novel Mutation in the Moesin (MSN) Gene Leads to Immunodeficiency with Epstein-Barr Virus (EBV) Infection and Dermatomyositis-Like Symptoms. In Journal of clinical immunology, 44, 155. doi:10.1007/s10875-024-01755-0. https://pubmed.ncbi.nlm.nih.gov/38922539/

2. Huang, Chien-Yu, Wei, Po-Li, Batzorig, Uyanga, Lee, Cheng-Chin, Chang, Yu-Jia. 2023. Identification of Moesin (MSN) as a Potential Therapeutic Target for Colorectal Cancer via the β-Catenin-RUNX2 Axis. In International journal of molecular sciences, 24, . doi:10.3390/ijms241310951. https://pubmed.ncbi.nlm.nih.gov/37446127/

3. Qin, Yuanyuan, Chen, Weilong, Jiang, Guojuan, Huang, Shenglin, Liu, Suling. 2020. Interfering MSN-NONO complex-activated CREB signaling serves as a therapeutic strategy for triple-negative breast cancer. In Science advances, 6, eaaw9960. doi:10.1126/sciadv.aaw9960. https://pubmed.ncbi.nlm.nih.gov/32128390/

4. Li, Muquan, Luo, Shuanghong, Zhuo, Zhiqiang, Shu, Min. 2023. Two cases of pediatric primary immunodeficiency caused by a familial moesin(MSN)gene mutation. In Clinical immunology (Orlando, Fla.), 258, 109858. doi:10.1016/j.clim.2023.109858. https://pubmed.ncbi.nlm.nih.gov/38052292/