Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation

被引：189
作者：
Kurtz, DM
Rinaldo, P
Rhead, WJ
Tian, LQ
Millington, DS
Vockley, J
Hamm, DA
Brix, AE
Lindsey, JR
Pinkert, CA
O'Brien, WE
Wood, PA
机构：
[1] Univ Alabama Birmingham, Dept Comparat Med, Sch Med, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Dept Comparat Med, Sch Dent, Birmingham, AL 35294 USA
[3] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
[4] Univ Iowa, Dept Pediat, Div Med Genet, Iowa City, IA 52242 USA
[5] Duke Univ, Childrens Hosp, Mass Spectrometry Facil, Res Triangle Pk, NC 27709 USA
[6] Mayo Clin & Mayo Fdn, Dept Med Genet, Rochester, MN 55905 USA
[7] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1998年 / 95卷 / 26期
关键词：
D O I：
10.1073/pnas.95.26.15592
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Abnormalities of fatty acid metabolism are recognized to play a significant role in human disease, but the mechanisms remain poorly understood. Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the initial step in mitochondrial fatty acid oxidation (FAO), We produced a mouse model of LCAD deficiency with severely impaired FAG. Matings between LCAD +/- mice yielded an abnormally low number of LCAD +/- and -/- offspring, indicating frequent gestational loss. LCAD -/- mite that reached birth appeared normal, but had severely reduced fasting tolerance with hepatic and cardiac lipidosis, hypoglycemia, elevated serum free fatty acids, and nonketotic dicarboxylic aciduria, Approximately 10% of adult LCAD -/- males developed cardiomyopathy, and sudden death was observed in 4 of 75 LCAD -/- mice. These results demonstrate the crucial roles of mitochondrial FAO and LCAD in vivo.
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页码：15592 / 15597
页数：6
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