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Mice without myoglobin

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Abstract

Myoglobin, an intracellular haemoprotein expressed in the heart and oxidative skeletal myofibres of vertebrates, binds molecular oxygen and may facilitate oxygen transport from erythrocytes to mitochondria, thereby maintaining cellular respiration during periods of high physiological demand1,2,3,4,5,6,7,8,9,10. Here we show, however, that mice without myoglobin, generated by gene-knockout technology, are fertile and exhibit normal exercise capacity and a normal ventilatory response to low oxygen levels (hypoxia). Heart and soleus muscles from these animals are depigmented, but function normally in standard assays of muscle performance invitro across a range of work conditions and oxygen availability. These data show that myoglobin is not required to meet the metabolic requirements of pregnancy or exercise in a terrestrial mammal, and raise new questions about oxygen transport and metabolic regulation in working muscles.

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Figure 1: Targeted disruption of the myoglobin gene.
Figure 2: Physiological assessments of intact animals.
Figure 3: Physiological assessments of isolated muscle preparations.

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Acknowledgements

We thank J. Shelton, M. Fina, C. Storey and A. Richman for technical assistance. This work was supported by grants from the NIH (to R.S.W., R.B.-D. & D.J.G.) and American Heart Association (to N.B.R.).

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Authors and Affiliations

  1. Departments of Internal Medicine, Dallas, 75235, Texas, USA

    Daniel J. Garry, Nina B. Radford, Eva R. Chin, Rhonda Bassel-Duby & R. Sanders Williams

  2. Departments of Physiology, Dallas, 75235, Texas, USA

    George A. Ordway & Robert W. Grange

  3. Departments of Molecular Biology/Oncology, University of Texas Southwestern Medical Center, Dallas, 75235, Texas, USA

    R. Sanders Williams

  4. Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, 45267, Ohio, USA

    John N. Lorenz

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  1. Daniel J. Garry
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  2. George A. Ordway
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  3. John N. Lorenz
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  4. Nina B. Radford
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  5. Eva R. Chin
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  6. Robert W. Grange
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  7. Rhonda Bassel-Duby
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  8. R. Sanders Williams
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Correspondence to R. Sanders Williams.

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Garry, D., Ordway, G., Lorenz, J. et al. Mice without myoglobin. Nature 395, 905–908 (1998). https://doi.org/10.1038/27681

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  • DOI: https://doi.org/10.1038/27681

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