A heterozygote phenotype is present in the jvs +/- mutant mouse livers.

The juvenile visceral steatosis (jvs) mouse, having a mutation in the carnitine transporter gene Octn2, is a model of primary systemic carnitine deficiency in humans (SCD, OMIM 212140). Like humans with SCD, homozygous jvs -/- mice have hepatic and cardiac steatoses, reduced plasma and tissue carnitines, and increased urinary carnitine clearance. Because symptomatic heterozygotes have been reported for some fatty acid oxidation disorders, including SCD, we compared the jvs heterozygotes to normal control mice. We measured the free and esterified carnitine, total cholesterol, and triglycerides in adult liver samples, myocardium, and skeletal muscle. Our results indicate significant differences between the livers of nonfasting adult normal (n = 8) vs jvs heterozygotes (n = 8) (means +/- SEM, p < 0.01) for the following parameters: free carnitine, 2.28 +/- 0.36 nmol/mg protein vs 0.41 +/- 0.13; total carnitine, 3.48 +/- 0.36 vs 1.27 +/- 0.25; triglycerides, 0.14 +/- 0.04 vs 0.39 +/- 0.02; and total cholesterol, 0.21 +/- 0.02 vs 0.39 +/- 0.04, but not for esterified carnitine, 1.18 +/- 0.17 vs 0.90 +/- 0.17 (p > 0.05). There is also a negative correlation between hepatic free carnitine and triglycerides from jvs heterozygotes (p < 0.05). Similar results were obtained with myocardium and skeletal muscle. We conclude that free and total carnitine levels are significantly lower in the heterozygote mouse liver and heart while triglyceride and total cholesterol levels are significantly higher. We speculate that in situations of lipolytic stress, some SCD heterozygotes might develop clinical symptoms of carnitine deficiency.