Abcg4-KO Mouse

Abcg4, a member of the ATP-binding cassette (ABC) transporter family, is predominantly expressed in the central nervous system (CNS) [3,4]. It is thought to transport cholesterol, oxysterols and cholesterol synthesis intermediates, and is implicated in maintaining sterol homeostasis in the brain [1]. Additionally, ABCG4 may be involved in amyloid-β export at the blood-brain barrier (BBB), and is associated with pathways related to neurodegenerative conditions like Alzheimer's disease (AD) [1].

In Ostrinia furnacalis, knockout of the ABCG4 gene using the CRISPR/Cas9 system led to higher resistance to Cry1 proteins, indicating it may act as a receptor for Bt Cry1 toxin [2]. In the APPswe,Ind (J9) mouse model of AD, Abcg4 knockout did not exacerbate the AD phenotype, as no differences were seen in behavioral tests, senile plaque numbers, or amyloid-β clearance [4]. In non-small-cell lung cancer (NSCLC) patients treated with cisplatin-based chemotherapy, high ABCG4 expression was associated with poor prognosis [5].

In conclusion, ABCG4 plays a role in multiple biological processes and disease conditions. Its function as a potential toxin receptor in insects, and its association with AD and NSCLC prognosis, as revealed through gene knockout models, provides valuable insights into these disease areas. Understanding ABCG4 may offer new directions for the treatment and prevention of related diseases.

References:

1. Yang, Alryel, Alrosan, Amjad Z, Sharpe, Laura J, Callaghan, Richard, Gelissen, Ingrid C. 2020. Regulation of ABCG4 transporter expression by sterols and LXR ligands. In Biochimica et biophysica acta. General subjects, 1865, 129769. doi:10.1016/j.bbagen.2020.129769. https://pubmed.ncbi.nlm.nih.gov/33141061/

2. Gao, Qing, Lin, Yaling, Wang, Xiuping, Zhang, Yongjun, Zhang, Tiantao. 2022. Knockout of ABC Transporter ABCG4 Gene Confers Resistance to Cry1 Proteins in Ostrinia furnacalis. In Toxins, 14, . doi:10.3390/toxins14010052. https://pubmed.ncbi.nlm.nih.gov/35051029/

3. Koshiba, S, An, R, Saito, H, Tamura, A, Ishikawa, T. . Human ABC transporters ABCG2 (BCRP) and ABCG4. In Xenobiotica; the fate of foreign compounds in biological systems, 38, 863-88. doi:10.1080/00498250801986944. https://pubmed.ncbi.nlm.nih.gov/18668433/

4. Fong, Vincent, Kanuri, Babunageswararao, Traubert, Owen, Lui, Min, Patel, Shailendra B. 2023. Behavioral and metabolic and effects of ABCG4 KO in the APPswe,Ind (J9) mouse model of Alzheimer's disease. In Research square, , . doi:10.21203/rs.3.rs-3014093/v1. https://pubmed.ncbi.nlm.nih.gov/37333297/

5. Yang, Guang, Wang, Xue-Jiao, Huang, Li-Jun, Li, Xiao-Fei, Zhang, Zhi-Pei. 2015. High ABCG4 Expression Is Associated with Poor Prognosis in Non-Small-Cell Lung Cancer Patients Treated with Cisplatin-Based Chemotherapy. In PloS one, 10, e0135576. doi:10.1371/journal.pone.0135576. https://pubmed.ncbi.nlm.nih.gov/26270652/