Generating Genetically Engineered Mouse Models

Ccr2^–/– mice (strain 004999) were obtained from The Jackson Laboratory. To generate KPC-CCR2^–/– mice, Kras^LSL-G12DPdx1-Cre (KC) mice were crossed with p53^LSL-R172H/+ or p53^{LSL-R172H/LSL-R172H} mice to generate KPC mice. We crossed CCR2^–/– mice with KC mice to generate KC-CCR2^–/– mice, and these were then crossed with p53^R172H/+ or p53^{LSL-R172H/LSL-R172H} mice to generate KPC-CCR2^–/– mice. The KPC-CCR2^–/– mice were of C57BL/6 background. KPC mice on the C57BL/6 background were used as the control for the comparative studies. The progeny were born in an expected Mendelian ration, with no obvious functional defects. In vivo drug studies were done using a KPC genetically engineered mouse model (68 (link)) on a mixed background as previously described. At the endpoint (or, for the early studies, at 10–11 weeks), full necropsies were performed on all study animals and included a gross examination of all organs for macroscopic disease as previously described (15 (link), 67 (link), 69 (link)).