Pik3ap1-KO Mouse

Pik3ap1, also known as B-cell adapter for PI3K (BCAP), plays a crucial role in the PI3K/AKT signaling pathway [1,3,5-8]. It is involved in regulating immune responses, cell proliferation, and inflammation, which are essential for maintaining normal physiological functions [1-4,6-9]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying its functions.

In macrophages, mice with macrophage-specific deletion of Pik3ap1 (BCAP) fail to recover from dextran sulfate sodium-induced colitis due to prolonged intestinal inflammation and impaired tissue repair. Absence of Pik3ap1 hinders inactivation of FOXO1 and GSK3β, leading to an enhanced inflammatory state. It also results in defective aerobic glycolysis, reduced lactate production, decreased histone lactylation, and decreased expression of reparative macrophage genes, indicating its role in the transition of inflammatory macrophages to reparative macrophages [1]. In GES-1 cells, Helicobacter pylori stimulation leads to hypermethylation of the Pik3ap1 promoter, down-regulating its expression. Intervention of Pik3ap1 inhibits the expression of downstream gene AKT and the immunoinflammatory gene IL-6, and promotes cell proliferation [2]. In the context of African swine fever virus (ASFV) infection, overexpression of Pik3ap1 significantly inhibits ASFV replication in vitro, independent of the PI3K-Akt pathway [3].

In summary, Pik3ap1 is a key regulator in multiple biological processes. Studies using KO/CKO mouse models have revealed its importance in inflammation resolution, tissue repair, and immune responses against infections. Its role in various disease conditions, such as colitis, gastric epithelial cell inflammation, and viral infections, highlights the potential of targeting Pik3ap1 for therapeutic interventions.

References:

1. Irizarry-Caro, Ricardo A, McDaniel, Margaret M, Overcast, Garrett R, Troutman, Ty Dale, Pasare, Chandrashekhar. 2020. TLR signaling adapter BCAP regulates inflammatory to reparatory macrophage transition by promoting histone lactylation. In Proceedings of the National Academy of Sciences of the United States of America, 117, 30628-30638. doi:10.1073/pnas.2009778117. https://pubmed.ncbi.nlm.nih.gov/33199625/

2. Zhang, Andong, Yan, Shiying, Cao, Mei, Hu, Guoku, Zhao, Jian. 2020. Abnormal methylation of PIK3AP1 was involved in regulating the immune inflammatory response of GES-1 cells induced by Helicobacter pylori. In Biochemical and biophysical research communications, 524, 36-42. doi:10.1016/j.bbrc.2020.01.007. https://pubmed.ncbi.nlm.nih.gov/31980170/

3. Yang, Bo, Hao, Yu, Yang, Jinke, Zheng, Haixue, Zhang, Keshan. 2023. PI3K-Akt pathway-independent PIK3AP1 identified as a replication inhibitor of the African swine fever virus based on iTRAQ proteomic analysis. In Virus research, 327, 199052. doi:10.1016/j.virusres.2023.199052. https://pubmed.ncbi.nlm.nih.gov/36775023/