“…The generation of a mouse knockout line is often the first step in developing a genetic mouse model. In cases where the full deletion is lethal, as with some high-confidence NDD genes ( Oliver and Davies, 2009 ; Schmidt et al, 2017 , 2022 ; Clarke et al, 2019 ; Jimenez et al, 2020 ), the heterozygous mutant can serve as a potential model. Notably, the HET genotype can be more reflective of mutant alleles in human disorders than null deletions ( Toma et al, 2014 ; Michetti et al, 2022 ), with the drawback that partial loss of a gene does not have the same impact as total knockout.…”