Of mice and men: from early NMR studies of the heart to physiological genomics

Just before I became an editor of Biochemical and Biophysical Research Communications in 1977 we published our first paper in this same journal on the study of tiny perfused rat hearts by (31)P NMR. In this article I trace the development of this in vivo NMR approach from the study of small rat and mouse hearts to human investigations. With the advent of molecular genetics the mouse became a key model organism for understanding and characterizing the function of human genes. I illustrate this by some of our recent work on Duchenne and Becker muscular dystrophy where the in vivo biochemical abnormalities observed in the human can be better understood from investigations of the muscle and heart of the murine model for muscular dystrophy, the mdx mouse. In particular, the mdx mouse heart exhibits ECG (conduction) abnormalities similar to that in the human which we associate with the reduction of the neuronal nitric oxide synthase activity compared to controls. We have also demonstrated in the mouse model that the increased sensitivity of the heart to ischemia is associated with a decrease in the insulin-stimulated glucose transport. Imaging techniques involving NMR, visible light, and others will play an increasingly important role in linking genomics to functional "molecular physiology." Copyright 1999 Academic Press.