Described herein are inbred B6 ES cell lines that exhibit high developmental capacities and have a number of advantages over ES cell lines already available. First, they can be used for gene targeting and have a high percentage of germline transmission when injected into diploid host blastocysts (˜50-80%). Second, these ES cell lines can successfully be used to generate live pups by tetraploid blastocyst complementation, producing a high percentage (15-20%) of mice that are entirely inbred B6 ES cell derived. Third, these ES cells lines can be used to rapidly generate mice that are homozygous for a gene of interest. These advantages indicate that the inbred B6 ES cells provided here facilitate the rapid generation of inbred B6 mouse models in a cost-effective and efficient manner.