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.