Pik3cd-KO Mouse

Pik3cd, which encodes p110δ, the catalytic subunit of PI3Kδ, is a crucial gene. Phosphoinositide 3-kinases (PI3Ks) signaling transduction, in which Pik3cd is involved, plays a critical role in various biological processes, such as angiogenesis, cell growth, and immune cell development [1,2]. The PI3K-AKT-mechanistic target of rapamycin pathway, where Pik3cd-encoded p110δ functions, is essential for normal cellular activities [4].

In a mouse model of oxygen-induced retinopathy, editing genomic Pik3cd with a recombinant dual adeno-associated viral (rAAV) system led to a significant decrease in p110δ expression, Akt activation, and pathological retinal angiogenesis, suggesting Pik3cd's role in abnormal retinal angiogenesis [2]. In glioblastoma, CRISPR/Cas9-mediated knockout of Pik3cd in U87-MG cells reduced cell migration, invasion, and colony formation abilities, and negated tumorigenesis in nude mice. Further study revealed that this was related to the impaired activity of PAK3 and PLEK2, indicating Pik3cd's oncogenic potential in glioblastoma [3].

In conclusion, Pik3cd is vital for processes like angiogenesis and cell growth regulation. Gene-editing in mouse models, such as KO in retinal cells and glioblastoma cells, has revealed its role in abnormal retinal angiogenesis and glioblastoma tumorigenesis. These findings suggest that Pik3cd could be a potential therapeutic target for related diseases.

References:

1. Lucas, Carrie L, Chandra, Anita, Nejentsev, Sergey, Condliffe, Alison M, Okkenhaug, Klaus. 2016. PI3Kδ and primary immunodeficiencies. In Nature reviews. Immunology, 16, 702-714. doi:10.1038/nri.2016.93. https://pubmed.ncbi.nlm.nih.gov/27616589/

2. Wu, Wenyi, Ma, Gaoen, Qi, Hui, Zhang, Shaochong, Lei, Hetian. . Genome Editing of Pik3cd Impedes Abnormal Retinal Angiogenesis. In Human gene therapy, 34, 30-41. doi:10.1089/hum.2022.079. https://pubmed.ncbi.nlm.nih.gov/36515172/

3. Shao, Wei, Azam, Zulfikar, Guo, Jintao, To, Shing Shun Tony. 2022. Oncogenic potential of PIK3CD in glioblastoma is exerted through cytoskeletal proteins PAK3 and PLEK2. In Laboratory investigation; a journal of technical methods and pathology, 102, 1314-1322. doi:10.1038/s41374-022-00821-8. https://pubmed.ncbi.nlm.nih.gov/35851857/

4. Edwards, Emily S J, Bier, Julia, Cole, Theresa S, Uzel, Gulbu, Tangye, Stuart G. 2018. Activating PIK3CD mutations impair human cytotoxic lymphocyte differentiation and function and EBV immunity. In The Journal of allergy and clinical immunology, 143, 276-291.e6. doi:10.1016/j.jaci.2018.04.030. https://pubmed.ncbi.nlm.nih.gov/29800648/