Anp32b, also known as acidic leucine-rich nuclear phosphoprotein 32B, is a protein-coding gene. It has multiple functions including acting as a histone chaperone [3]. It is involved in various biological processes and pathways, such as being essential for viral RNA genome replication of avian influenza A viruses (IAVs) [1], regulating p53 signaling in hematopoietic cells [2], and controlling the chromatin incorporation of the histone variant macroH2A [3].

In knockout (KO) or conditional knockout (CKO) mouse models, Anp32b deficiency has diverse effects. In hematopoietic cells, conditional deletion of Anp32b impairs the repopulation and post-injury regeneration of hematopoietic stem cells (HSCs) and enhances p53 transcriptional activity, which impairs leukemic stem cell (LSC) function in a murine chronic myelogenous leukemia (CML) model [2]. In B-cell acute lymphoblastic leukemia (B-ALL) mouse models, conditional deletion of Anp32b in hematopoietic cells promotes leukemogenesis, as Anp32b normally interacts with and enhances the transcriptional activity of PU.1 in B-ALL cells [4]. Also, Anp32b -/- mice show severe defects in ocular development due to repression of Pax6 [5]. Moreover, ANP32B -/- mice infected with influenza A virus (IAV) have reduced virus loads, inflammatory cytokine response, and pathogenicity compared to ANP32B +/+ mice [6]. In prostate cancer, knockdown of ANP32B in cell lines inhibits cell growth [7].

In summary, Anp32b is crucial in multiple biological processes. Studies using KO or CKO mouse models have revealed its significance in diseases like CML, B-ALL, ocular developmental defects, and influenza virus pathogenesis. These models help in understanding the role of Anp32b in specific disease areas, providing insights for potential therapeutic strategies [2,4,5,6,7].

References:

1. Staller, Ecco, Carrique, Loïc, Swann, Olivia C, Grimes, Jonathan M, Fodor, Ervin. 2024. Structures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation. In Nature communications, 15, 4123. doi:10.1038/s41467-024-48470-3. https://pubmed.ncbi.nlm.nih.gov/38750014/

2. Yang, Shuo, Zhu, Xiao-Na, Zhang, Hui-Lin, Chen, Guo-Qiang, Yu, Yun. . ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells. In Blood, 138, 2485-2498. doi:10.1182/blood.2020010400. https://pubmed.ncbi.nlm.nih.gov/34359074/

3. Mandemaker, Imke K, Fessler, Evelyn, Corujo, David, Mattiroli, Francesca, Ladurner, Andreas G. 2023. The histone chaperone ANP32B regulates chromatin incorporation of the atypical human histone variant macroH2A. In Cell reports, 42, 113300. doi:10.1016/j.celrep.2023.113300. https://pubmed.ncbi.nlm.nih.gov/37858472/

4. Yang, Qian, Liu, Hao-Ran, Yang, Shuo, Chen, Guo-Qiang, Yu, Yun. 2023. ANP32B suppresses B-cell acute lymphoblastic leukemia through activation of PU.1 in mice. In Cancer science, 114, 2882-2894. doi:10.1111/cas.15822. https://pubmed.ncbi.nlm.nih.gov/37137487/

5. Wei, Yu-Sheng, Liu, Hao-Ran, Yang, Qian, Zhi, Zhe, Yu, Yun. 2024. Anp32b Deficiency Suppresses Ocular Development by Repression of Pax6. In Ophthalmic research, 67, 644-653. doi:10.1159/000542447. https://pubmed.ncbi.nlm.nih.gov/39504945/

6. Beck, Sebastian, Zickler, Martin, Pinho Dos Reis, Vinícius, Stanelle-Bertram, Stephanie, Gabriel, Gülşah. 2020. ANP32B Deficiency Protects Mice From Lethal Influenza A Virus Challenge by Dampening the Host Immune Response. In Frontiers in immunology, 11, 450. doi:10.3389/fimmu.2020.00450. https://pubmed.ncbi.nlm.nih.gov/32231671/

7. Zhou, Cheng, Ma, Hangbin, Yu, Wandong, Zhang, Jun, Shi, Guowei. 2024. ANP32B inhibition suppresses the growth of prostate cancer cells by regulating c-Myc signaling. In Biochemical and biophysical research communications, 698, 149543. doi:10.1016/j.bbrc.2024.149543. https://pubmed.ncbi.nlm.nih.gov/38266312/