Abcg2-KO Mouse

ABCG2, also known as breast cancer resistance protein (BCRP), is an ATP-binding cassette transporter. It functions as a poly-specific efflux pump, transporting a wide range of substrates including xenobiotics, drugs, and metabolites out of cells. It is involved in multiple biological processes such as protecting the body from harmful substances by acting as a part of self-defence mechanisms in tissues like the intestine, blood-brain barrier, and placenta [3,5,6]. It also plays a role in drug pharmacokinetics and is linked to multidrug resistance in tumors [2,4,5,6]. Genetic models like knockout mouse models are valuable for studying its functions.

In macrophages, ABCG2 exports itaconate from the cytosol to the extracellular space in an ATPase-dependent manner. ABCG2-mediated itaconate export limits transcription factor TFEB-dependent lysosomal biogenesis and antibacterial innate immunity. In a mouse model of S. typhimurium infection, deficiency of ABCG2-mediated itaconate export in macrophages promotes antibacterial innate immune defense [1].

In conclusion, ABCG2 is a crucial transporter with diverse functions. Model-based research, especially using KO mouse models, has revealed its role in limiting antibacterial innate immunity in macrophages. Understanding ABCG2 functions has potential implications for treating bacterial infections and also for addressing issues like multidrug resistance in acute myeloid leukemia and other cancers [1,2].

References:

1. Chen, Chao, Zhang, Zhenxing, Liu, Caiyun, Liu, Ping, Li, Xinjian. 2024. ABCG2 is an itaconate exporter that limits antibacterial innate immunity by alleviating TFEB-dependent lysosomal biogenesis. In Cell metabolism, 36, 498-510.e11. doi:10.1016/j.cmet.2023.12.015. https://pubmed.ncbi.nlm.nih.gov/38181789/

2. Damiani, Daniela, Tiribelli, Mario. 2023. ABCG2 in Acute Myeloid Leukemia: Old and New Perspectives. In International journal of molecular sciences, 24, . doi:10.3390/ijms24087147. https://pubmed.ncbi.nlm.nih.gov/37108308/

3. Robey, Robert W, To, Kenneth K K, Polgar, Orsolya, Dean, Michael, Bates, Susan E. 2008. ABCG2: a perspective. In Advanced drug delivery reviews, 61, 3-13. doi:10.1016/j.addr.2008.11.003. https://pubmed.ncbi.nlm.nih.gov/19135109/

4. Chandratre, Sharayu, Olsen, Jordyn, Howley, Richard, Chen, Bin. 2023. Targeting ABCG2 transporter to enhance 5-aminolevulinic acid for tumor visualization and photodynamic therapy. In Biochemical pharmacology, 217, 115851. doi:10.1016/j.bcp.2023.115851. https://pubmed.ncbi.nlm.nih.gov/37858868/

5. Wiese, Michael. 2015. BCRP/ABCG2 inhibitors: a patent review (2009-present). In Expert opinion on therapeutic patents, 25, 1229-37. doi:10.1517/13543776.2015.1076796. https://pubmed.ncbi.nlm.nih.gov/26291461/

6. Hasanabady, Maryam Hosseini, Kalalinia, Fatemeh. . ABCG2 inhibition as a therapeutic approach for overcoming multidrug resistance in cancer. In Journal of biosciences, 41, 313-24. doi:. https://pubmed.ncbi.nlm.nih.gov/27240991/