To more fully understand the necessity of ERK1/2 signaling for cardiac hypertrophy we generated cardiac specific ERK1/2 targeted mice: Erk1–/–; Erk2 fl/fl and used two different Cre recombinase lines- the Nkx2.5 knock-in Cre or the α-Myosin heavy chain transgenic Cre to eliminate both ERK1 and ERK2 from cardiomyocytes in the heart (Kehat et al., 2011). This evidence concerns the gene MAPK3 and cardiac hypertrophy.