Myoglobin, an intracellular haemoprotein expressed in the heart and ox
idative skeletal myofibres of vertebrates, binds molecular oxygen and
may facilitate oxygen transport from erythrocytes to mitochondria, the
reby maintaining cellular respiration during periods of high physiolog
ical demand(1-10). Here we show, however, that mice without myoglobin,
generated by gene-knockout techhnology, are fertile and exhibit norma
l exercise capacity and a normal ventilatory response to low oxygen le
vels (hypoxia). Heart and soleus muscles from these animals are depigm
ented, but function normally in standard assays of muscle performance
in vitro across a range of work conditions and oxygen availability. Th
ese data show that myoglobin is not required to meet the metabolic req
uirements of pregnancy or exercise in a terrestrial mammal, and raise
new questions about oxygen transport and metabolic regulation in worki
ng muscles.