Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS mice as a model of human carnitine transporter deficiency.
Recently, the marked decline in renal carnitine reabsorption has been thought to account fotr the systemic carnitine deficiency in juvenile visceral steatosis (JVS) mice. We have conducted a kinetic analysis using embryonic fibroblasts derived from normal, heterozygous, and homozygous jvs mice and found that the high-affinity carnitine transporter (Km = 5.5 microM), which shows Na+ and temperature dependency and stereospecificity, is defective in homozygous jvs mice. Moreover, a gene dose-dependent decrease of carnitine transport activity, which was due to a decrease in the number of the transporter molecules, was found in heterozygous jvs mice. Similar phenomena have been observed in human primary carnitine deficiency. Therefore, JVS mice may be useful for understanding this extremely rare human hereditary disorder.
Hashimoto
N
N
Institute for Experimental Animals, Faculty of Medicine, Kanazawa University, Japan.
Suzuki
F
F
Tamai
I
I
Nikaido
H
H
Kuwajima
M
M
Hayakawa
J
J
Tsuji
A
A
D000818:Animals; D001692:Biological Transport; D002331:Carnitine / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D018628:Gene Dosage; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007700:Kinetics; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains
D002352:Carrier Proteins; D002331:Carnitine