Notably, strains with combined Prkdc (scid) and Il2rg (null) mutations—such as NOG and NSG mice— are widely used due to their profound immunodeficiency, allowing efficient engraftment of various human cells. However, these models were generated by disrupting the Il2rg gene through replacement with a neomycin resistance (Neo) cassette in embryonic stem cells. Here, PRKDC is linked to Immunodeficiency.