Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS mice as a model of human carnitine transporter deficiency

被引:32
作者
Hashimoto, N
Suzuki, F
Tamai, I
Nikaido, H
Kuwajima, M
Hayakawa, JI [1 ]
Tsuji, A
机构
[1] Kanazawa Univ, Fac Med, Inst Expt Anim, Kanazawa, Ishikawa 920, Japan
[2] Kanazawa Univ, Fac Pharmaceut Sci, Dept Pharmaceut, Kanazawa, Ishikawa 920, Japan
[3] Hiroshima Univ, Res Inst Radiat Biol & Med, Hiroshima 734, Japan
[4] Univ Tokushima, Sch Med, Dept Lab Med, Tokushima 770, Japan
关键词
systemic carnitine deficiency; JVS mouse; membrane transporter; embryonic fibroblast; uptake kinetics;
D O I
10.1016/S0006-2952(97)00670-9
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Recently, the marked decline in renal carnitine reabsorption has been thought to account for 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 jus mice and found that the high affinity carnitine transporter (K-m = 5.5 mu M), 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 jus 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. (C) 1998 Elsevier Science Inc.
引用
收藏
页码:1729 / 1732
页数:4
相关论文
共 16 条
[1]  
Christodoulou J, 1996, AM J MED GENET, V66, P21, DOI 10.1002/(SICI)1096-8628(19961202)66:1<21::AID-AJMG5>3.3.CO
[2]  
2-H
[3]   HEREDITARY DEFECT IN CARNITINE MEMBRANE-TRANSPORT IS EXPRESSED IN SKIN FIBROBLASTS [J].
ERIKSSON, BO ;
LINDSTEDT, S ;
NORDIN, I .
EUROPEAN JOURNAL OF PEDIATRICS, 1988, 147 (06) :662-663
[4]   PRIMARY CARNITINE DEFICIENCY - HETEROZYGOTE AND INTRAFAMILIAL PHENOTYPIC VARIATION [J].
GARAVAGLIA, B ;
UZIEL, G ;
DWORZAK, F ;
CARRARA, F ;
DIDONATO, S .
NEUROLOGY, 1991, 41 (10) :1691-1693
[5]   CARDIAC-HYPERTROPHY IN JUVENILE VISCERAL STEATOSIS (JVS) MICE WITH SYSTEMIC CARNITINE DEFICIENCY [J].
HORIUCHI, M ;
YOSHIDA, H ;
KOBAYASHI, K ;
KURIWAKI, K ;
YOSHIMINE, K ;
TOMOMURA, M ;
KOIZUMI, T ;
NIKAIDO, H ;
HAYAKAWA, J ;
KUWAJIMA, M ;
SAHEKI, T .
FEBS LETTERS, 1993, 326 (1-3) :267-271
[6]  
HORIUCHI M, 1992, J BIOL CHEM, V267, P5032
[7]   PRIMARY DEFECT OF JUVENILE VISCERAL STEATOSIS (JVS) MOUSE WITH SYSTEMIC CARNITINE DEFICIENCY IS PROBABLY IN RENAL CARNITINE TRANSPORT-SYSTEM [J].
HORIUCHI, M ;
KOBAYASHI, K ;
YAMAGUCHI, S ;
SHIMIZU, N ;
KOIZUMI, T ;
NIKAIDO, H ;
HAYAKAWA, J ;
KUWAJIMA, M ;
SAHEKI, T .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1994, 1226 (01) :25-30
[8]   INFANTILE DISEASE WITH MICROVESICULAR FATTY INFILTRATION OF VISCERA SPONTANEOUSLY OCCURRING IN THE C3H-H-2-DEGREE STRAIN OF MOUSE WITH SIMILARITIES TO REYES-SYNDROME [J].
KOIZUMI, T ;
NIKAIDO, H ;
HAYAKAWA, J ;
NONOMURA, A ;
YONEDA, T .
LABORATORY ANIMALS, 1988, 22 (01) :83-87
[9]   ANIMAL-MODEL OF SYSTEMIC CARNITINE DEFICIENCY - ANALYSIS IN C3H-H-2-DEGREES STRAIN OF MOUSE ASSOCIATED WITH JUVENILE VISCERAL STEATOSIS [J].
KUWAJIMA, M ;
KONO, N ;
HORIUCHI, M ;
IMAMURA, Y ;
ONO, A ;
INUI, Y ;
KAWATA, S ;
KOIZUMI, T ;
HAYAKAWA, J ;
SAHEKI, T ;
TARUI, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 174 (03) :1090-1094
[10]   Carnitine transport defect in fibroblasts of juvenile visceral steatosis (JVS) mouse [J].
Kuwajima, M ;
Lu, KM ;
Harashima, H ;
Ono, A ;
Sato, I ;
Mizuno, A ;
Murakami, T ;
Nakajima, H ;
Miyagawa, J ;
Namba, M ;
Hanafusa, T ;
Hayakawa, J ;
Matsuzawa, Y ;
Shima, K .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 223 (02) :283-287