Psmb9-KO Mouse

Psmb9, also known as proteasome 20S subunit beta 9, is a subunit of the immunoproteasome. The immunoproteasome is involved in various cell processes, such as cell survival or death decisions, the cell cycle, and cellular differentiation [3]. It is also associated with the antigen processing and presentation pathway, which is crucial for the immune system [6].

In melanoma, overexpression of Psmb9 in cell lines mimicking the hypomethylated state inhibited cell proliferation and migration, suggesting it acts as a tumor suppressor by activating CD8+ T cells, modulating IFN-γ secretion, and influencing IFN-γ receptors [1]. In atherosclerosis, Psmb9 deficiency in Apoe-/- mice decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation, and PSMB8-AS1 aggravated atherosclerosis via a Psmb9 -dependent mechanism [2]. For urothelial bladder carcinoma, the Psmb9 rs17587 SNP was associated with an increased risk of the disease [3]. In coal workers' pneumoconiosis, Psmb9 was identified as a susceptibility gene, and overexpression of Psmb9 abolished silica-induced cell apoptosis [4]. Variants in Psmb9 were also found to differentially affect Parkinson's disease risk in GBA and LRRK2 mutation carriers [5], and the Psmb9 rs17587 SNP increased the risk of vitiligo in the Saudi community [6]. In uterine leiomyosarcoma, the immunoproteasome pathway including Psmb9 was upregulated, and high CD8+/Psmb9 ratio was associated with better overall survival [7].

In conclusion, Psmb9 is an important gene involved in multiple biological processes and diseases. Gene knockout and related functional studies in various animal models, especially mouse models, have revealed its role in tumorigenesis, inflammation-related diseases, and neurodegenerative diseases. These findings provide insights into the pathogenesis of these diseases and potential targets for treatment.

References:

1. Hu, Xing, Hu, Zhengang, Zhang, Hao, Zhang, Chi, Cheng, Quan. 2023. Deciphering the tumor-suppressive role of PSMB9 in melanoma through multi-omics and single-cell transcriptome analyses. In Cancer letters, 581, 216466. doi:10.1016/j.canlet.2023.216466. https://pubmed.ncbi.nlm.nih.gov/37944578/

2. Li, Shu, He, Run-Chao, Wu, Shao-Guo, Dai, Xiaoyan, Hu, Yan-Wei. 2023. LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis. In Circulation research, 134, 60-80. doi:10.1161/CIRCRESAHA.122.322360. https://pubmed.ncbi.nlm.nih.gov/38084631/

3. Elhawary, Nasser A, Ekram, Samar N, Abumansour, Iman S, Nassir, Anmar M, Mufti, Ahmad H. 2023. Sequence Variants in PSMB8/PSMB9 Immunoproteasome Genes and Risk of Urothelial Bladder Carcinoma. In Cureus, 15, e36293. doi:10.7759/cureus.36293. https://pubmed.ncbi.nlm.nih.gov/36937130/

4. Yuan, Jiali, Wang, Ting, Wang, Lijuan, Zhang, Qunwei, Ni, Chunhui. 2022. Transcriptome-wide association study identifies PSMB9 as a susceptibility gene for coal workers' pneumoconiosis. In Environmental toxicology, 37, 2103-2114. doi:10.1002/tox.23554. https://pubmed.ncbi.nlm.nih.gov/35506645/

5. Shani, Shachar, Goldstein, Orly, Gana-Weisz, Mali, Alcalay, Roy N, Orr-Urtreger, Avi. 2023. Variants in PSMB9 and FGR differentially affect Parkinson's disease risk in GBA and LRRK2 mutation carriers. In Parkinsonism & related disorders, 111, 105398. doi:10.1016/j.parkreldis.2023.105398. https://pubmed.ncbi.nlm.nih.gov/37116292/

6. Mufti, Ahmad H, AlJahdali, Imad A, Elhawary, Nasser A, Alharbi, Amaal, Tayeb, Mohammed T. 2021. Variations in TAP1 and PSMB9 Genes Involved in Antigen Processing and Presentation Increase the Risk of Vitiligo in the Saudi Community. In International journal of general medicine, 14, 10031-10044. doi:10.2147/IJGM.S341079. https://pubmed.ncbi.nlm.nih.gov/34984025/

7. Maia Falcão, Raul, Kokaraki, Georgia, De Wispelaere, Wout, Carlson, Joseph Woodward, Petta, Tirzah Braz. 2022. The Expression of the Immunoproteasome Subunit PSMB9 Is Related to Distinct Molecular Subtypes of Uterine Leiomyosarcoma. In Cancers, 14, . doi:10.3390/cancers14205007. https://pubmed.ncbi.nlm.nih.gov/36291793/