Comparative analysis of two new zebrafish models: The cyp1a low-expression line and cyp1a knockout line under PAHs exposure

Cytochrome P450 1 (CYP1) is an important enzyme family involved in the metabolism of pollutants, and used as a biomarker to monitor environmental pollution. In this study, a fluorescence-labeled cyp1a zebrafish line, named as KI ( cyp1a +/+ -T2A-mCherry) (KICM), was originally constructed to monitor dioxin-like compounds in the environment. However, the cyp1a gene expression in the KICM line was inhibited by the fluorescence labeling, thus leading to a significantly increased sensitivity of KICM zebrafish line to PAHs. Then, a cyp1a knockout zebrafish line, named KOC, were constructed for comparative analysis with the cyp1a low-expression line. Interestingly, knockout of the cyp1a gene did not increase the sensitivity of zebrafish to PAHs as significantly as the cyp1a low-expression line. So, the expression levels of related genes in the aryl hydrocarbon receptor pathway were analyzed and the results showed that the expression level of cyp1b in KOC group was significantly higher than that of wild type and KICM under the same PAH exposure. This indicated that the effect of losing cyp1a was compensated by inducing expression of cyp1b . In conclusion, two new zebrafish models including cyp1a low-expression line and cyp1a knockout line were constructed in this study, which may provide a convenient model for subsequent studies on the toxicity mechanism of PAHs and the role of cyp1a in detoxification.