Hnf4aos-KO Mouse

Hnf4aos, the mouse homolog of human HNF4A-AS1, is a long non-coding RNA. HNF4A-AS1/Hnf4aos is involved in regulating the expression of cytochrome P450 (CYP) 3A4, which is crucial for the metabolism of drugs like ritonavir. It is also associated with the ubiquitination pathway related to hepatocyte nuclear factor 4 alpha (HNF4A) [1,2].

In a mouse model, liver-specific knockdown of Hnf4aos led to increased serum aspartate and alanine transaminase levels, enlarged and degenerated hepatocytes, and increased endoplasmic reticulum stress markers 24 hours after ritonavir administration. This was due to heightened Cyp3a11 (homolog of human CYP3A4) expression, indicating Hnf4aos plays a role in protecting against ritonavir-induced hepatotoxicity [1].

In conclusion, Hnf4aos is essential in regulating CYP3A4 expression, and its knockdown in mouse models reveals its protective role against ritonavir-induced liver injury. The study of Hnf4aos in KO mouse models contributes to understanding the mechanism of drug-induced hepatotoxicity, providing insights into potential strategies for preventing such liver damage [1].

References:

1. Wang, Xiaofei, Wang, Zijing, Wang, Jingya, Wang, Pei, Zhang, Lirong. 2025. Role of HNF4A-AS1/HNRNPC-mediated HNF4A ubiquitination protection against ritonavir-induced hepatotoxicity. In Molecular pharmacology, 107, 100021. doi:10.1016/j.molpha.2025.100021. https://pubmed.ncbi.nlm.nih.gov/40037142/

2. Guo, Shangdong, Lu, Hong. 2018. Novel mechanisms of regulation of the expression and transcriptional activity of hepatocyte nuclear factor 4α. In Journal of cellular biochemistry, 120, 519-532. doi:10.1002/jcb.27407. https://pubmed.ncbi.nlm.nih.gov/30191603/