Letters to Nature

Nature 395, 905-908 (29 October 1998) | doi:10.1038/27681; Received 25 June 1998; Accepted 8 September 1998

Mice without myoglobin

Daniel J. Garry1, George A. Ordway2, John N. Lorenz3, Nina B. Radford1, Eva R. Chin1, Robert W. Grange2, Rhonda Bassel-Duby1 & R. Sanders Williams1,4

  1. Departments of Internal Medicine, Dallas, Texas 75235, USA
  2. Departments of Physiology, Dallas, Texas 75235, USA
  3. Departments of Molecular Biology/Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA
  4. Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio 45267, USA

Correspondence to: R. Sanders Williams1,4 Correspondence and requests for materials should be addressed to R.S.W. (e-mail: Email: williams@ryburn.swmed.edu).

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.