Bmx-KO Mouse

Bmx, also known as Bone marrow kinase on chromosome X, is a cytosolic tyrosine kinase and a member of the TEC kinase family. It plays diverse roles in biological processes. In the immune response, Bmx is expressed in hematopoietic cells of the myeloid lineage. It is also involved in the response to ischemia and pressure overload in the endocardium and cardiac endothelium. In cancer, Bmx has been shown to mediate the survival and tumorigenicity of glioblastoma cancer stem cells. Bmx regulates the secretion of proinflammatory cytokines induced by TNFα, IL-1β, and TLR agonists in the inflammatory response, and is required for the activation of the MAP kinase and NFκB pathways [1].

In cecal ligation and puncture models of sepsis, Bmx-KO mice showed increased lung injury, inflammation, and thrombin-mediated endothelial permeability. Bmx specifically repressed thrombin-PAR1 signaling in endothelial cells by directly phosphorylating PAR1 and promoting its internalization and deactivation, thus protecting against vascular leakage during early sepsis [2]. In a mouse model of arthritis, Bmx deficiency conferred protection, and genetic replacement with a kinase-inactive allele restored susceptibility, suggesting that in vivo Bmx kinase activity can be dispensable [1]. In retinal ischemia/reperfusion injury experiments using Bmx-/-mice, Bmx knockdown mitigated negative impacts on retinal tissue structure and visual function, reduced apoptosis, and suppressed inflammatory responses through down-regulating phosphorylation of the AKT/ERK/STAT3 pathway [3].

In conclusion, Bmx is crucial in inflammation, cardiovascular disease, and cancer. Gene knockout mouse models have revealed its roles in these areas, such as its function in maintaining endothelial integrity during sepsis, its dispensable kinase activity in arthritis, and its impact on retinal injury. These findings contribute to understanding the biological functions of Bmx and may provide potential targets for related disease treatments.

References:

1. Cenni, Bruno, Gutmann, Sascha, Gottar-Guillier, Marie. . BMX and its role in inflammation, cardiovascular disease, and cancer. In International reviews of immunology, 31, 166-73. doi:10.3109/08830185.2012.663838. https://pubmed.ncbi.nlm.nih.gov/22449076/

2. Li, Zhao, Yin, Mingzhu, Zhang, Haifeng, Zhou, Huanjiao Jenny, Min, Wang. 2020. BMX Represses Thrombin-PAR1-Mediated Endothelial Permeability and Vascular Leakage During Early Sepsis. In Circulation research, 126, 471-485. doi:10.1161/CIRCRESAHA.119.315769. https://pubmed.ncbi.nlm.nih.gov/31910739/

3. Huang, Guangyi, Zhang, Shaoyang, Liao, Jing, Wei, Yantao, Xu, Fan. 2024. BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade. In Heliyon, 10, e27114. doi:10.1016/j.heliyon.2024.e27114. https://pubmed.ncbi.nlm.nih.gov/38434304/