Short CommunicationGene-Dose Effect on Carnitine Transport Activity in Embryonic Fibroblasts of JVS Mice as a Model of Human Carnitine Transporter Deficiency
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Animals
JVS mice were originally found among mice of the C3H.OH strain in our laboratory (Institute for Experimental Animals, Faculty of Medicine, Kanazawa University). The autosomal recessive mutant gene jvs was then back-crossed into C57BL/6J mice (Clea Japan), and this congenic strain was called “B6-jvs.” Animals were maintained under semi-barrier conditions at 24.0 ± 2.0° with a 12:12 hr light–dark cycle in compliance with the standards set forth in the “Guidelines for the Care and Use of
Carnitine Specific Transporter
Uptake of l-carnitine in immortalized normal mouse embryonic fibroblasts was temperature-dependent and linear for up to 4 hr and had a saturable, substrate concentration-dependent component at 37° (data not shown). This saturable uptake of l-carnitine showed both Na+-dependence (Fig. 1) and stereospecificity (Fig. 2). These observations indicate that l-carnitine uptake occurs via a carnitine-specific transporter-mediated process in normal mouse embryonic fibroblasts.
Kinetic Analysis of Concentration-Dependent Carnitine Transport
Carnitine uptake by
Discussion
Recently, a prenatal diagnosis of human carnitine transporter defect was attempted in a fetus at high risk of having this disorder [13]. In this and some other case studies of primary carnitine-deficiency patients, the defect of carnitine transport activities showed autosomal recessive inheritance (i.e. the parents or nonaffected brother of affected patients showed transport activities intermediate between patients and control) 14, 15.
The JVS mouse was found as a mutant mouse with a hereditary
Acknowledgements
This work was supported, in part, by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan (No. 08458274) and the Ono Pharmaceutical Co., Ltd.
References (15)
- et al.
Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of urea cycle enzymes by normalizing their transcription
J Biol Chem
(1992) - et al.
Abnormal expression of urea cycle enzyme genes in juvenile visceral steatosis (jvs) mice
Biochim Biophys Acta
(1992) - et al.
Abnormal gene expression and regulation in the liver of jvs mice with systemic carnitine deficiency
Biochim Biophys Acta
(1994) - et al.
Animal model of systemic carnitine deficiencyAnalysis in C3H-H-20 strain of mouse associated with juvenile visceral steatosis
Biochem Biophys Res Commun
(1991) - et al.
Cardiac hypertrophy in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency
FEBS Lett
(1993) - et al.
Primary defect of juvenile visceral steatosis (jvs) mouse with systemic carnitine deficiency is probably in renal carnitine transport system
Biochim Biophys Acta
(1994) - et al.
Carnitine transport defect in fibroblasts of juvenile visceral steatosis (JVS) mouse
Biochem Biophys Res Commun
(1996)
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