MAPK3 and Splenomegaly: Indeed, macroscopic examination of tamoxifen-treated Vhlfloxed-UBC-Cre-ERT2 mice revealed marked splenomegaly, an indicator of increased activity of the oxygen-VHL/PHD/HIF sensing pathway, as seen in Phd2 deficient and Phd1:Phd3 double knock-out mice [19].