MITOCHONDRIAL ABNORMALITIES IN A MARINE MODEL OF PRIMARY CARNITINE DEFICIENCY - SYSTEMIC PATHOLOGY AND TRIAL OF REPLACEMENT THERAPY

Mitochondrial abnormalities and effectiveness of replacement therapy w ere examined in a murine model of systemic carnitine deficiency, namel y the juvenile visceral steatosis (JVS) mouse. Homozygous JVS mice rev ealed severe lipid deposition and abnormal mitochondria in liver, hear t, skeletal muscle, and kidney, but there was no pathological change i n the nervous system, though they showed cerebral signs. There were nu merous ragged-red fibers in muscles, but enzyme activities of the resp iratory chain were intact. Histograms of oxidative and nonoxidative mu scle 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 immu nostaining 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 i n untreated mice.