Bax, also known as Bcl-2-associated X protein, is a critical executioner in the mitochondrial regulated cell death pathway. It functions by permeabilizing the mitochondrial outer membrane (MOM), releasing apoptotic signaling molecules, which is essential for maintaining tissue homeostasis [1,2]. Dysregulation of Bax can lead to aberrant cell death, and thus is associated with various diseases such as cancer, neurodegeneration, and heart failure [2]. Gene knockout (KO) mouse models have been valuable in studying Bax's role.

In Ku70-knockout mice, Bax-induced apoptosis shortens their lifespan by inducing emphysema, suggesting that Bax-mediated apoptosis has a significant impact on lifespan shortening in DNA repair-defective mice [3]. In Bax-depleted mouse retinal ganglion cells (RGCs), the cells survive and become quiescent following optic nerve damage, indicating that lowering Bax quantity is neuroprotective after acute injury [5]. Also, in a glaucoma model using Bax-/-mice, Bax contributes to RGC dendritic degeneration, distinguishing the proximal and distal neurodegenerative programs during glaucoma progression [4].

In conclusion, Bax plays a vital role in regulating cell death and maintaining tissue homeostasis. The use of Bax KO/CKO mouse models has revealed its significance in diseases like emphysema, neurodegeneration in the context of optic nerve damage and glaucoma. Understanding Bax's function through these models provides insights into the mechanisms of disease occurrence, potentially offering new strategies for disease treatment and prevention.

References:

1. Spitz, Adam Z, Gavathiotis, Evripidis. 2021. Physiological and pharmacological modulation of BAX. In Trends in pharmacological sciences, 43, 206-220. doi:10.1016/j.tips.2021.11.001. https://pubmed.ncbi.nlm.nih.gov/34848097/

2. Zhang, Zhenwei, Hou, Linghui, Liu, Dan, Huang, Min, Zhao, Linxiang. 2024. Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges. In Acta pharmaceutica Sinica. B, 14, 2378-2401. doi:10.1016/j.apsb.2024.02.010. https://pubmed.ncbi.nlm.nih.gov/38828138/

3. Matsuyama, Shigemi, Palmer, James, Bates, Adam, Ngo, Justine, Matsuyama, Mieko. . Bax-induced apoptosis shortens the life span of DNA repair defect Ku70-knockout mice by inducing emphysema. In Experimental biology and medicine (Maywood, N.J.), 241, 1265-71. doi:10.1177/1535370216654587. https://pubmed.ncbi.nlm.nih.gov/27302174/

4. Risner, Michael L, Pasini, Silvia, McGrady, Nolan R, Calkins, David J. 2022. Bax Contributes to Retinal Ganglion Cell Dendritic Degeneration During Glaucoma. In Molecular neurobiology, 59, 1366-1380. doi:10.1007/s12035-021-02675-5. https://pubmed.ncbi.nlm.nih.gov/34984584/

5. Donahue, Ryan J, Maes, Margaret E, Grosser, Joshua A, Nickells, Robert W. 2019. BAX-Depleted Retinal Ganglion Cells Survive and Become Quiescent Following Optic Nerve Damage. In Molecular neurobiology, 57, 1070-1084. doi:10.1007/s12035-019-01783-7. https://pubmed.ncbi.nlm.nih.gov/31673950/