Pik3cd Knockout mouse models

Expression of p110 delta, encoded by Pik3cd and orthologous to human PIK3CD, is largely restricted to leukocytes, where it couples the B cell receptor, T cell receptor and cytokine receptors through p85 to PIP3 production, AKT activation and FOXO1 inactivation, controlling B cell development, class switch recombination, T cell differentiation and neutrophil chemotaxis. Human gain-of-function substitutions, notably E1021K in the carboxy-terminal kinase domain, cause activated PI3K delta syndrome with senescent effector T cells, lymphoproliferation and impaired humoral immunity, while biallelic loss produces primary immunodeficiency. Two complementary alleles dominate the field: the catalytically inactive D910A knockin, which preserves protein and complex stoichiometry while abolishing lipid kinase output, and Cre-dependent E1021K knockins that reproduce the hyperactive human state in a lineage-restricted manner. Because germline deletion is viable, lethality is not limiting, and endpoints such as germinal center formation and idelalisib response map cleanly onto the chosen allele class.

A conventional Pik3cd knockout removes gene function in all cells that inherit the allele. It is a proven first pass for target validation when redundancy is low.