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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kurtz, DM; Rinaldo, P; Rhead, WJ; Tian, L; Millington, DS; Vockley, J; Hamm, DA; Brix, AE; Lindsey, JR; Pinkert, CA; O'Brien, WE; Wood, PA

Published Date

  • December 22, 1998

Published In

Volume / Issue

  • 95 / 26

Start / End Page

  • 15592 - 15597

PubMed ID

  • 9861014

Pubmed Central ID

  • PMC28088

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.95.26.15592


  • eng

Conference Location

  • United States