CRISPR/Cas9 genome editing is used to alter embryonic stem (ES) cells from Krastm4Tyj mutant mice. The original Kras mice have a G12D point mutation in exon 2 of the gene and a loxP ite flanked STOP element in intron 1. Guide RNAs targeting the KrasG12D site, an ssODN template and the Cas9 nuclease are used to introduce a p.G12R mutation (c.34_36delGGTinsCGA), commonly seen in pancreatic ductal adenocarcinoma. (J:299292)