Phenotypic analysis of gene-specific knockout (KO) mice hasrevolutionized our understanding of in vivo gene functions. Asthe use of mouse embryonic stem (ES) cells is inevitable forconventional gene targeting, the generation of knockout miceremains a very time-consuming and expensive process. Toaccelerate the large-scale production and phenotype analyses ofKO mice, international efforts have organized global consortiasuch as the International Knockout Mouse Consortium (IKMC)and International Mouse Phenotype Consortium (IMPC), andthey are persistently expanding the KO mouse catalogue that ispublicly available for the researches studying specific genes ofinterests in vivo. However, new technologies, adoptingzinc-finger nucleases (ZFNs) or Transcription Activator-LikeEffector (TALE) Nucleases (TALENs) to edit the mouse genome,are now emerging as valuable and effective shortcuts alternativefor the conventional gene targeting using ES cells. Here, weintroduce the recent achievement of IKMC, and evaluate thesignificance of ZFN/TALEN technology in mouse genetics.