Mitochondrial abnormalities in a murine model of primary carnitine deficiency. Systemic pathology and trial of replacement therapy.

Mitochondrial abnormalities and effectiveness of replacement therapy were examined in a murine model of systemic carnitine deficiency, namely the juvenile visceral steatosis (JVS) mouse. Homozygous JVS mice revealed severe lipid deposition and abnormal mitochondria in liver, heart, skeletal muscle, and kidney, but there was no pathological change in the nervous system, though they showed cerebral signs. There were numerous ragged-red fibers in muscles, but enzyme activities of the respiratory chain were intact. Histograms of oxidative and nonoxidative muscle fibers showed an increase in small and oxidative muscle fibers in 4-week-old JVS mice, but this difference no longer existed in 8-week- or 1-year-old JVS mice. On the contrary, Mn-superoxide dismutase immunostaining of muscle showed a focal increase in every age of JVS mice. With L-carnitine treatment, JVS mice could survive for a year, but to some extent, there were the same pathological changes as those seen in untreated mice.