Apobec1-KO Mouse

Apobec1, a member of the AID/APOBECs family, is a cytidine (C) to uridine (U) RNA-editing enzyme. It is physiologically involved in C>U RNA editing, with the apolipoprotein B (ApoB) transcript being a well-characterized target in humans. By editing a CAA codon in ApoB mRNA into a stop codon, it regulates cholesterol metabolism [2,4]. Apobec1 requires cofactors like A1CF and RBM46 to form an “editosome” for its RNA-editing activity [2].

In mice, studies on gene-modified models have provided insights into Apobec1's role. In A1cf-/-mice, there were minimal changes in hepatic and intestinal apoB RNA editing, while Rbm47 liver-specific knockout (Rbm47LKO) mice showed reduced editing in some RNA targets including apoB. Intestine-specific Rbm47 knockout (Rbm47IKO) mice had a more significant reduction in apoB RNA editing. Double knockout of A1cf and Rbm47 in liver (ARLKO) eliminated apoB RNA editing and reduced editing in most other targets. These suggest that A1CF and RBM47 interact in a tissue-specific manner to regulate Apobec1-dependent C-to-U RNA editing [3]. Also, in A1cf + / Tg mice (with hepatocyte-specific A1cf-transgenic overexpression), the development of hepatic steatosis, fibrosis, and hepatocellular cancer (HCC) was observed, and this was independent of Apobec1 [1].

In conclusion, Apobec1 is crucial for C>U RNA editing, especially in regulating ApoB mRNA and cholesterol metabolism. The study of Apobec1-related gene-knockout mouse models has revealed its role in tissue-specific RNA editing and the development of liver-related diseases such as hepatic steatosis, fibrosis, and HCC. Understanding Apobec1's function can provide insights into disease mechanisms and potential therapeutic targets [1,3].

References:

1. Blanc, Valerie, Riordan, Jesse D, Soleymanjahi, Saeed, Roberts, Lewis R, Davidson, Nicholas O. . Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer. In The Journal of clinical investigation, 131, . doi:10.1172/JCI138699. https://pubmed.ncbi.nlm.nih.gov/33445170/

2. Wang, Shanshan, Kim, Kyumin, Gelvez, Nicolas, Vermulst, Marc, Chen, Xiaojiang S. 2023. Identification of RBM46 as a novel APOBEC1 cofactor for C-to-U RNA-editing activity. In Journal of molecular biology, 435, 168333. doi:10.1016/j.jmb.2023.168333. https://pubmed.ncbi.nlm.nih.gov/38708190/

3. Blanc, Valerie, Xie, Yan, Kennedy, Susan, Nadeau, Joseph H, Davidson, Nicholas O. 2018. Apobec1 complementation factor (A1CF) and RBM47 interact in tissue-specific regulation of C to U RNA editing in mouse intestine and liver. In RNA (New York, N.Y.), 25, 70-81. doi:10.1261/rna.068395.118. https://pubmed.ncbi.nlm.nih.gov/30309881/

4. Chieca, Martina, Torrini, Serena, Conticello, Silvestro G. . Live-Cell Quantification of APOBEC1-Mediated RNA Editing: A Comparison of RNA Editing Assays. In Methods in molecular biology (Clifton, N.J.), 2181, 69-81. doi:10.1007/978-1-0716-0787-9_5. https://pubmed.ncbi.nlm.nih.gov/32729075/