Fig. 6: Deletion of Vhl slows primary tumor growth and decreases total tumor burden.

a Survival analysis of Vhlf/f PyMT+ and Vhl−/− PyMT+ mice where end point represents sacrifice due to tumor size reaching collection threshold. Log-rank test. b–d Comparison of the age at sacrifice, total burden at sacrifice, and number of tumors collected per mouse. Two-tailed Mann–Whitney test. e Quantitative PCR analysis of Vhl expression compared to B2m from whole-tumor homogenate RNA. Expression is normalized to the mean of the f/f control group. Two-tailed Mann–Whitney test. f Schematic of PCR-based validation of Vhl locus recombination using a three-primer PCR reaction. Genomic DNA was used as the input material. DNA electrophoresis gel represents the PCR products from the reactions depicted in the schematic diagram. The lower molecular weight of the band in the Vhl−/− lanes indicate successful recombination. The residual band in the Vhl−/− lanes are likely from non-recombined stromal cells present in the tumor. g–k Quantitative PCR analysis of HIF target genes (Vegfa, Pgk1, Glut1, Tek, Pdgfb) compared to B2m from whole-tumor homogenate RNA. Two-tailed Mann–Whitney test. Graphs represent mean per group and error bars represent s.e.m. n = 20 Vhlf/f PyMT+ mice, n = 19 (or 18 in e–k) Vhl−/− PyMT+ mice.