Varying susceptibility to myocardial infarction among C57BL/6 mice of different genetic background

Genetically manipulated mouse lines are invaluable to investigate the effects of a single gene on sensitivity to ischemia. When choosing appropriate controls, we were concerned that intrinsic, strain-independent but colony-dependent differences may influence the susceptibility to ischemia. We, therefore, compared the infarct:risk volume ratio (I:R%) after 30-min global ischemia in Langendorff-perfused hearts from outbred C57BL/6 mice with that in wild-type mice derived from heterozygote × heterozygote crosses of two different in-house C57BL/6 mouse lines with targeted disruption of an MKK3 or MAPKAPK2 allele. Despite similar hemodynamic characteristics, I:R% in outbred C57BL/6 hearts was significantlysmaller (40.8 ± 2.8%) than in C57BL/6 MAPKAPK2 wild types (65.8 ± 4.5%, P = 0.0003) and significantly larger than in C57BL/6 MKK3 wild types (23.7 ± 2.9%, P = 0.002). Therefore, inherent colony substrain-dependent differences appear to influence the susceptibility to infarction in response to global ischemia, underscoring the importance of using colony-matched wild-type controls in murine studies of myocardial ischemia.