Bco1-KO Mouse

Bco1, also known as β-Carotene 15,15'-dioxygenase, is a key enzyme in carotenoid metabolism. It catalyzes the oxidative cleavage of the central 15,15' carbon-carbon double bond of β-carotene, converting provitamin A carotenoids to vitamin A. This process is crucial for maintaining normal physiological functions related to vision, lipid and energy metabolism, and immune cell differentiation [1].

In Bco1 null mice, studies have shown that the production of vitamin A from β-carotene is disrupted. This implicates Bco1-mediated vitamin A production in the effects of β-carotene on atherosclerosis resolution, as β-carotene can accelerate atherosclerosis resolution in wild-type mice but not in Bco1-deficient mice [2]. Also, ablation of both Bco1 and Bco2 in double knockout mice led to hepatic steatosis, indicating that Bco1 plays a role in maintaining normal hepatic lipid and cholesterol homeostasis, potentially through the regulation of the farnesoid X receptor/miR-34a/sirtuin 1 pathway [3].

In conclusion, Bco1 is essential for the conversion of provitamin A carotenoids to vitamin A, and its function is closely related to lipid and cholesterol metabolism in the body. Gene knockout mouse models, especially those related to Bco1, have provided valuable insights into its role in diseases such as atherosclerosis and hepatic steatosis, helping us to understand the underlying mechanisms of these diseases and potentially paving the way for new treatment strategies.

References:

1. Harrison, Earl H, Kopec, Rachel E. 2020. Enzymology of vertebrate carotenoid oxygenases. In Biochimica et biophysica acta. Molecular and cell biology of lipids, 1865, 158653. doi:10.1016/j.bbalip.2020.158653. https://pubmed.ncbi.nlm.nih.gov/32035229/

2. Pinos, Ivan, Coronel, Johana, Albakri, Asma'a, Fisher, Edward A, Amengual, Jaume. 2024. β-Carotene accelerates the resolution of atherosclerosis in mice. In eLife, 12, . doi:10.7554/eLife.87430. https://pubmed.ncbi.nlm.nih.gov/38319073/

3. Lim, Ji Ye, Liu, Chun, Hu, Kang-Quan, Smith, Donald E, Wang, Xiang-Dong. 2018. Ablation of carotenoid cleavage enzymes (BCO1 and BCO2) induced hepatic steatosis by altering the farnesoid X receptor/miR-34a/sirtuin 1 pathway. In Archives of biochemistry and biophysics, 654, 1-9. doi:10.1016/j.abb.2018.07.007. https://pubmed.ncbi.nlm.nih.gov/30006135/