Anp32a-KO Mouse

Anp32a, also known as acidic leucine-rich nuclear phosphoprotein-32A, is an essential host protein involved in multiple biological processes. It plays a role in histone acetylation, regulating gene expression. It is also a crucial co-factor for the influenza virus polymerase, influencing viral replication [6,1,2,5,7].

In Anp32a-deficient mouse models, Wnt signaling was hyper-activated in articular cartilage and the heart. Mechanistically, ANP32A inhibits Wnt target gene expression via histone acetylation masking, and its deficiency led to more severe osteoarthritis and cardiac hypertrophy phenotypes. Treatment with a Wnt inhibitor and an antioxidant could alleviate some of these phenotypes [3]. In zebrafish embryos, knockdown of Anp32a reduced spinal cord regeneration and swimming capability after spinal cord injury, indicating its positive role in neuronal regeneration [4]. In colorectal cancer cells, ANP32A knockdown attenuated migration, invasion, and epithelial-mesenchymal transition (EMT) by suppressing β-catenin and phosphorylated-ERK expression [8]. In hepatocellular carcinoma, silencing of ANP32A inhibited cell proliferation, migration, and invasion, while overexpression promoted these processes, and it acts through the HMGA1/STAT3 pathway [9].

In conclusion, Anp32a is involved in histone acetylation, regulation of Wnt signaling, and has significant impacts on diseases like osteoarthritis, heart disease, and various cancers. Gene-knockout or knockdown models in mice and zebrafish have been instrumental in uncovering its role in these biological processes and disease conditions, providing insights for potential therapeutic strategies.

References:

1. Carrique, Loïc, Fan, Haitian, Walker, Alexander P, Fodor, Ervin, Grimes, Jonathan M. 2020. Host ANP32A mediates the assembly of the influenza virus replicase. In Nature, 587, 638-643. doi:10.1038/s41586-020-2927-z. https://pubmed.ncbi.nlm.nih.gov/33208942/

2. Na, Lei, Sun, Liuke, Yu, Mengmeng, Lin, Yuezhi, Wang, Xiaojun. 2024. Avian ANP32A incorporated in avian influenza A virions promotes interspecies transmission by priming early viral replication in mammals. In Science advances, 10, eadj4163. doi:10.1126/sciadv.adj4163. https://pubmed.ncbi.nlm.nih.gov/38295177/

3. Monteagudo, S, Cornelis, F M F, Wang, X, Meulenbelt, I, Lories, R J. 2022. ANP32A represses Wnt signaling across tissues thereby protecting against osteoarthritis and heart disease. In Osteoarthritis and cartilage, 30, 724-734. doi:10.1016/j.joca.2022.02.615. https://pubmed.ncbi.nlm.nih.gov/35227892/

4. Lee, Hung-Chieh, Lai, Wei-Lin, Lin, Cheng-Yung, Chou, Tze-Bin, Tsai, Huai-Jen. 2022. Anp32a Promotes Neuronal Regeneration after Spinal Cord Injury of Zebrafish Embryos. In International journal of molecular sciences, 23, . doi:10.3390/ijms232415921. https://pubmed.ncbi.nlm.nih.gov/36555564/

5. Peacock, Thomas P, Swann, Olivia C, Salvesen, Hamish A, Long, Jason S, Barclay, Wendy S. 2020. Swine ANP32A Supports Avian Influenza Virus Polymerase. In Journal of virology, 94, . doi:10.1128/JVI.00132-20. https://pubmed.ncbi.nlm.nih.gov/32269123/

6. Yang, Xuejing, Lu, Bin, Sun, Xueqin, Wang, Qian-Fei, Huang, Zan. 2018. ANP32A regulates histone H3 acetylation and promotes leukemogenesis. In Leukemia, 32, 1587-1597. doi:10.1038/s41375-018-0010-7. https://pubmed.ncbi.nlm.nih.gov/29467488/

7. Fodor, Ervin, Te Velthuis, Aartjan J W. 2020. Structure and Function of the Influenza Virus Transcription and Replication Machinery. In Cold Spring Harbor perspectives in medicine, 10, . doi:10.1101/cshperspect.a038398. https://pubmed.ncbi.nlm.nih.gov/31871230/

8. Li, Xiaojuan, Li, Xumei, Liu, Guoxiang, Chen, Xu, Wang, Juan. 2023. ANP32A Knockdown Attenuates the Malignant Biological Behavior of Colorectal Cancer Cells by Suppressing Epithelial-mesenchymal Transition and ERK Activation. In Journal of Cancer, 14, 2759-2770. doi:10.7150/jca.84687. https://pubmed.ncbi.nlm.nih.gov/37781083/

9. Tian, Zilu, Liu, Zhiyi, Fang, Xiaokang, Shi, Hengliang, Wang, Renhao. . ANP32A promotes the proliferation, migration and invasion of hepatocellular carcinoma by modulating the HMGA1/STAT3 pathway. In Carcinogenesis, 42, 493-506. doi:10.1093/carcin/bgaa138. https://pubmed.ncbi.nlm.nih.gov/33332531/