A 31P-magnetic resonance spectroscopy and biochemical study of the mo(vbr) mouse: potential model for the mitochondrial encephalomyopathies.
Tracey I., Dunn JF., Radda GK.
31P-magnetic resonance spectroscopy (31P-MRS) provides new biochemical information on mitochondrial disorders affecting brain and muscle. To elucidate the mechanisms of mitochondrial abnormalities, however, animal models are needed. We assessed the mo(vbr) (mottled viable brindled) mouse for its value in studying (1) energetics of a mitochondrial disorder and (2) 31P-MRS changes associated with mitochondrial abnormalities in vivo. The maximal activity of succinate-cytochrome c reductase was significantly reduced in mo(vbr) muscle compared to controls, whereas cytochrome oxidase activity was only reduced in mo(vbr) brain. 31P-MRS of mo(vbr) brain showed an increased pH, but no changes in any metabolite ratios. The phosphocreatine (PCr) recovery rate after exercise was reduced in muscles from mo(vbr) mice, indicating impairment of oxidative metabolism. We conclude that mo(vbr) brain and muscle tissue have biochemical abnormalities consistent with mitochondrial impairment. The PCr recovery rate, measured by 31P-MRS, was sensitive to the muscle abnormality. This strain is best described as having chronic mitochondrial dysfunction.