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Vol. 96, Issue 18, 10495-10500, August 31, 1999
* Institut für Herz und Kreislaufphysiologie, Communicated by Ewald R. Weibel, University of Bern,
Herrenschwanden, Switzerland, July 15, 1999 (received for review February 4, 1999)
Myoglobin may serve a variety of functions in muscular oxygen
supply, such as O2 storage, facilitated
O2 diffusion, and myoglobin-mediated oxidative
phosphorylation. We studied the functional consequences of a myoglobin
deficiency on cardiac function by producing myoglobin-knockout (myo
Copyright © 1999 by The National Academy of Sciences 0027-8424/99/9610495-6$2.00/0
Physiology
Disruption of myoglobin in mice induces multiple
compensatory mechanisms
,
,,§
Institut
für Anatomie und Hirnforschung, and
Biologisch-Medizinisches
Forschungszentrum, Heinrich-Heine-Universität
Düsseldorf, Postfach 101007, 40001 Düsseldorf, Germany
/) mice. To genetically inactivate the myoglobin
gene, exon 2 encoding the heme binding site was deleted in embryonic
stem cells via homologous recombination. Myo/ mice
are viable, fertile, and without any obvious signs of functional limitations. Hemoglobin concentrations were significantly elevated in
myo/ mice. Cardiac function and energetics were
analyzed in isolated perfused hearts under resting conditions and
during 
-adrenergic stimulation with dobutamine.
Myo/ hearts showed no alteration in contractile
parameters either under basal conditions or after maximal
-adrenergic stimulation (200 nM dobutamine). Tissue levels of ATP,
phosphocreatine (31P-NMR), and myocardial O2
consumption were not altered. However, coronary flow {6.4 ± 1.3 ml·min1·g1 [wild-type (WT)] vs.
8.5 ± 2.4 ml·min1·g1
[myo/]} and coronary reserve [17.1 ± 2.1 (WT) vs. 20.8 ± 1.1 (myo/)
ml·min1·g1 were significantly
elevated in myo/ hearts. Histological examination
revealed that capillary density also was increased in
myo/ hearts [3,111 ± 400 mm2
(WT) vs. 4,140 ± 140 mm2
(Myo/)]. These data demonstrate that disruption of
myoglobin results in the activation of multiple compensatory mechanisms
that steepen the pO2 gradient and reduce the diffusion path
length for O2 between capillary and the mitochondria; this
suggests that myoglobin normally is important for the delivery of oxygen.
§
To whom reprint requests should be addressed. E-mail:
schrader{at}uni-duesseldorf.de.
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