Citations 1
Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation
Rinaldo, Piero, Rhead, William J., Tian, Liqun, Millington, David S., Vockley, Jerry , Hamm, Doug A., Brix, Amy E., Lindsey, J. Russell, Pinkert, Carl A. , O’Brien, William E., Kurtz, David M. , Wood, Philip A.
Proceedings of the National Academy of Sciences | July 26, 2002 | Volume: 95 | Issue: 26 | Pages: 15592-15597
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 FAO. Matings between LCAD +/− mice yielded an abnormally low number of LCAD +/− and −/− offspring, indicating frequent gestational loss. LCAD −/− mice 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 .