Genetically Modified Mouse Models of Prostate Cancer

In our studies we used TgAPT₁₂₁ mice (TgAPT₁₂₁^+/−, C57BL/6 × DBA/2 background) (19 (link)) bred to male B6D2F1 mice (Jackson Laboratories, Bar Harbor, ME). This model has probasin promoter driven, prostate epithelial cell-specific expression of a truncated SV40 Large T antigen protein that inactivates pRb family proteins. It has strong histologic similarities to the earlier stages of human prostate cancer (i.e. demonstrating hyperplasia, PIN, and adenocarcinoma over 6 months). Other mouse models used include mice with a floxed exon 2 in the Vdr gene (Vdr^fl/fl; C57BL/6) (18 (link)); mice with Cre recombinase expression driven by the rat probasin promoter (PB-Cre^+/−; C57BL/6) (NCI Mouse Models of Human Cancer Consortium, # 01XF5; Frederick, MD); and Vdr knockout mice with intestine-specific transgenic expression of the human VDR gene (C57BL/6) (20 (link)). Mice were genotyped as previously described (18 (link)–21 (link)). Mice were housed with a 12 h light/12 h dark cycle, in shoebox cages with individual ventilation. Lights were covered with a UVB filter (Pegasus Associates Lighting, Beaver, PA). Diets and water were fed ad libitum. Except for Experiment 4, mice were fed AIN-76A diet (1000 IU vitamin D₃/kg diet (22 (link))). All experiments were approved by either the Purdue University or the Ohio State University Animal Care and Use Committees.