Ms4a1-KO Mouse

Ms4a1, also known as the gene encoding B cell surface marker CD20, is a member of the membrane-spanning 4A (MS4A) family. It has a tetraspan structure and is differentially expressed in immunocompetent cells. It may associate with and modulate the signaling activity of different immunoreceptors, playing important roles in homeostasis, immunity, and disease [4].

In colorectal cancer, MS4A1 is significantly downregulated in carcinoma tissues, and its expression level is positively correlated with patient survival. A CD8+CD20+ subset of T cells, which exists in non-neoplastic colon but disappears in tumors, may function in host cancer immunosurveillance, and the tumor microenvironment suppresses this T subset through a PD-L1-dependent mechanism [1]. In breast cancer, MS4A1 expression can indicate lipid metabolism situation and reflect the immune microenvironment status. It is negatively correlated with patient age, clinical stage, etc., and positively correlated with the abundance of some immune cells. It has the potential to be an independent prognostic indicator [2]. In colon cancer, high expression of MS4A1 is associated with longer overall survival, and overexpression of MS4A1 can weaken the proliferation, migration, and invasion abilities of colon cancer cells. It can also be used as a marker to predict the sensitivity of patients with colon cancer to immunotherapy [3].

In summary, Ms4a1 is closely related to the immune microenvironment and prognosis in cancers such as colorectal and breast cancer. Its dysregulation may contribute to tumor progression. Research on Ms4a1 knockout or conditional knockout mouse models could potentially further clarify its functions in these disease processes, providing insights for targeted therapies.

References:

1. Mudd, T William, Lu, Chunwan, Klement, John D, Liu, Kebin. 2020. MS4A1 expression and function in T cells in the colorectal cancer tumor microenvironment. In Cellular immunology, 360, 104260. doi:10.1016/j.cellimm.2020.104260. https://pubmed.ncbi.nlm.nih.gov/33352466/

2. Li, Shilin, Fang, Yi. 2022. MS4A1 as a Potential Independent Prognostic Factor of Breast Cancer Related to Lipid Metabolism and Immune Microenvironment Based on TCGA Database Analysis. In Medical science monitor : international medical journal of experimental and clinical research, 28, e934597. doi:10.12659/MSM.934597. https://pubmed.ncbi.nlm.nih.gov/35091527/

3. Song, Ye, Zhang, Zhipeng, Zhang, Bo, Zhang, Weihui. 2022. CD8+ T cell-associated genes MS4A1 and TNFRSF17 are prognostic markers and inhibit the progression of colon cancer. In Frontiers in oncology, 12, 941208. doi:10.3389/fonc.2022.941208. https://pubmed.ncbi.nlm.nih.gov/36203424/

4. Mattiola, Irene, Mantovani, Alberto, Locati, Massimo. 2021. The tetraspan MS4A family in homeostasis, immunity, and disease. In Trends in immunology, 42, 764-781. doi:10.1016/j.it.2021.07.002. https://pubmed.ncbi.nlm.nih.gov/34384709/