Adaptive mechanisms that preserve cardiac function in mice without myoglobin

Mice lacking myoglobin survive to adulthood and meet the circulatory demand s of exercise and pregnancy without cardiac decompensation. In the present study, we show that many myoglobin-deficient embryos die in utero at midges tation with signs of cardiac failure. Fetal mice that survive to gestationa l day 12.5, however, suffer no subsequent excess mortality. Survival in the absence of myoglobin is associated with increased vascularity and the indu ction of genes encoding the hypoxia-inducible transcription factors 1 alpha and 2, stress proteins such as heat shock protein 27, and vascular endothe lial growth factor. These adaptations are evident in late fetal life, persi st into adulthood, and are sufficient to maintain normal myocardial oxygen consumption during stressed conditions. These data reveal that myoglobin is necessary to support cardiac function during development, but adaptive res ponses evoked in some animals can fully compensate for the defect in cellul ar oxygen transport resulting from the loss of myoglobin.