PRIMARY DEFECT OF JUVENILE VISCERAL STEATOSIS (JVS) MOUSE WITH SYSTEMIC CARNITINE DEFICIENCY IS PROBABLY IN RENAL CARNITINE TRANSPORT-SYSTEM

We investigated the reabsorptional system for carnitine in the kidney to elucidate the mechanism of carnitine deficiency in juvenile visceral steatosis (jus) mice. Jus mice had a higher rate of carnitine excretion at 10 days after birth than the controls, in spite of having no pathological acylcarnitine excretion in the urine. In an experiment to assay the uptake of carnitine using kidney slices, homozygous mutants showed significantly lower rates of Na-dependent carnitine uptake than controls. Heterozygous mice showed values of transport activity intermediate between homozygous mutants and homozygous controls. Scatchard plots (transport activity versus transport activity/carnitine concentration) revealed that the homozygous mutants had a defect in the high affinity site (K-m = 58 mu M) in the Na-dependent carnitine transport system in the kidney. These results indicate that the primary defect of jus mice is most probably related to the system for reabsorption of carnitine in the kidney.