Cyp4a12b-KO Mouse

Cyp4a12b, a member of the cytochrome P450 4A subfamily, is involved in the metabolism of arachidonic acid, specifically in the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), which is pro-inflammatory. It is also associated with pathways like the PPAR signaling pathway, and its expression can influence lipid metabolism [4,2]. Genetic mouse models are valuable for studying its functions in vivo.

In multiple studies, Cyp4a12b expression was found to be significantly altered in various disease-related scenarios. For instance, in mice intragastrically exposed to titanium dioxide nanoparticles, the significant change in Cyp4a12b expression led to severe oxidative stress, suggesting its potential as a biomarker for kidney toxicity [1]. In a mouse model of bronchial asthma, Gerberae Piloselloides Herba treatment modulated the PPAR signaling pathway, affecting Cyp4a12b expression, which in turn regulated lipid metabolism disorder, decreased inflammatory mediators, and alleviated lung injury [2]. Maternal exposure to broccoli sprouts in a transgenic mouse model induced gene and methylation changes in Cyp4a12b, correlated with preventing offspring mammary cancer [3]. In acute inflammation in mice, LPS administration led to suppressed Cyp4a12b mRNA levels and 20-HETE formation in the liver and kidney, indicating an isoform-and tissue-dependent role in altering eicosanoid metabolism [4].

In conclusion, Cyp4a12b is crucial in processes such as lipid metabolism, oxidative stress response, and inflammation. Findings from mouse models have revealed its significant roles in diseases like kidney toxicity, bronchial asthma, and mammary cancer prevention, highlighting its potential as a therapeutic target or biomarker in these disease areas.

References:

1. Gui, Suxin, Sang, Xuezi, Zheng, Lei, Hong, Fashui, Tang, Meng. 2013. Intragastric exposure to titanium dioxide nanoparticles induced nephrotoxicity in mice, assessed by physiological and gene expression modifications. In Particle and fibre toxicology, 10, 4. doi:10.1186/1743-8977-10-4. https://pubmed.ncbi.nlm.nih.gov/23406204/

2. Liu, Chunhua, Fu, Changli, Lu, Yuan, Huang, Yong, Li, Yongjun. 2024. Integration of metabolomics and transcriptomics to reveal the mechanism of Gerberae piloselloidis herba in alleviating bronchial asthma. In Journal of ethnopharmacology, 325, 117852. doi:10.1016/j.jep.2024.117852. https://pubmed.ncbi.nlm.nih.gov/38307356/

3. Arora, Itika, Sharma, Manvi, Li, Shizhao, Li, Yuanyuan, Tollefsbol, Trygve O. 2022. An integrated analysis of the effects of maternal broccoli sprouts exposure on transcriptome and methylome in prevention of offspring mammary cancer. In PloS one, 17, e0264858. doi:10.1371/journal.pone.0264858. https://pubmed.ncbi.nlm.nih.gov/35263365/

4. Theken, Katherine N, Deng, Yangmei, Kannon, M Alison, Poloyac, Samuel M, Lee, Craig R. 2010. Activation of the acute inflammatory response alters cytochrome P450 expression and eicosanoid metabolism. In Drug metabolism and disposition: the biological fate of chemicals, 39, 22-9. doi:10.1124/dmd.110.035287. https://pubmed.ncbi.nlm.nih.gov/20947618/