The B6-hIL23A mouse is a humanized model generated by gene editing, in which the mouse Il23a genomic sequence is replaced with the corresponding sequence from the human IL23A gene, while preserving the endogenous sequence encoding the mouse IL23p19 signal peptide (aa. 1-21). Homozygous B6-hIL23A mice are viable and fertile, and suitable for investigating the pathomechanisms and therapeutic interventions of immune-related diseases and cancer, as well as for screening and developing IL23A-targeted therapeutics, and for preclinical pharmacodynamic and safety evaluations.