Cyp7b1-KO Mouse

Cyp7b1, cytochrome P450 family 7 subfamily B member 1, is a key enzyme in alternative cholesterol metabolism. It hydroxylates carbons 6 and 7 of the B ring of oxysterols and steroids, reducing their biological activity and facilitating excretion. This is crucial for inactivating oxysterols and converting them into bile salts in the liver [1]. It is also involved in cholesterol metabolism pathways, and its functions are vital for normal physiological processes in the liver, reproductive tract, and brain [1]. Genetic models, like KO mouse models, have been instrumental in studying its functions.

In KO mouse models, CYP7B1 deficiency significantly attenuates experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis, by reducing leukocyte infiltration, suppressing pathogenic CD4+ T cell proliferation, and decreasing myeloid cell activation [2]. BM-MSCs from CYP7B1 conditional knockout (CKO) mice have impaired activation abilities, relating to delayed bone defect healing [3]. Cyp7b1 -/- mice exposed to cold have compromised brown adipose tissue (BAT) function, reduced fecal bile acid levels, and decreased BAT-mediated clearance of fatty acids from triglyceride-rich lipoproteins [4]. At thermoneutrality, Cyp7b1 -/- mice fed a choline-deficient high-fat diet show aggravated metabolic-associated fatty liver disease (MAFLD) with higher plasma alanine aminotransferase activity, hyperlipidemia, and increased liver fibrosis [5].

In conclusion, Cyp7b1 is essential for cholesterol metabolism, playing a significant role in various physiological processes. Studies using KO/CKO mouse models have revealed its functions in diseases such as multiple sclerosis, bone defect healing, BAT-mediated lipid clearance, and MAFLD. These models have provided valuable insights into the mechanisms underlying these disease conditions, highlighting Cyp7b1 as a potential therapeutic target.

References:

1. Stiles, Ashlee R, McDonald, Jeffrey G, Bauman, David R, Russell, David W. 2009. CYP7B1: one cytochrome P450, two human genetic diseases, and multiple physiological functions. In The Journal of biological chemistry, 284, 28485-9. doi:10.1074/jbc.R109.042168. https://pubmed.ncbi.nlm.nih.gov/19687010/

2. Song, Huanhuan, Lv, Aowei, Zhu, Zhibao, Wang, Ning, Fu, Ying. 2024. CYP7B1 deficiency impairs myeloid cell activation in autoimmune disease of the central nervous system. In PNAS nexus, 3, pgae334. doi:10.1093/pnasnexus/pgae334. https://pubmed.ncbi.nlm.nih.gov/39262855/

3. Zhang, Zhaoqiang, Su, Zepeng, Li, Zhikun, Shen, Huiyong, Xie, Zhongyu. 2024. CYP7B1-mediated 25-hydroxycholesterol degradation maintains quiescence-activation balance and improves therapeutic potential of mesenchymal stem cells. In Cell chemical biology, 31, 1277-1289.e7. doi:10.1016/j.chembiol.2024.01.009. https://pubmed.ncbi.nlm.nih.gov/38382532/

4. Evangelakos, Ioannis, Kuhl, Anastasia, Baguhl, Miriam, Heeren, Joerg, Worthmann, Anna. 2022. Cold-Induced Lipoprotein Clearance in Cyp7b1-Deficient Mice. In Frontiers in cell and developmental biology, 10, 836741. doi:10.3389/fcell.2022.836741. https://pubmed.ncbi.nlm.nih.gov/35478959/

5. Evangelakos, Ioannis, Schwinge, Dorothee, Worthmann, Anna, Scheja, Ludger, Heeren, Joerg. 2021. Oxysterol 7-α Hydroxylase (CYP7B1) Attenuates Metabolic-Associated Fatty Liver Disease in Mice at Thermoneutrality. In Cells, 10, . doi:10.3390/cells10102656. https://pubmed.ncbi.nlm.nih.gov/34685636/