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

Publication ,  Journal Article
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 in: Proc Natl Acad Sci U S A
December 22, 1998
Published version (DOI) Link to item

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.

Duke Scholars

David Stuart Millington
Author David Stuart Millington Pediatrics, Medical Genetics

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.95.26.15592

ISSN

0027-8424

Publication Date

December 22, 1998

Volume

95

Issue

26

Start / End Page

15592 / 15597

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Muscle, Skeletal
  • Mitochondria, Liver
  • Mice, Knockout
  • Mice
  • Liver
  • Lipid Metabolism, Inborn Errors
  • Humans
  • Fatty Acids, Nonesterified
  • Disease Models, Animal
 

Citation

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Kurtz, D. M., Rinaldo, P., Rhead, W. J., Tian, L., Millington, D. S., Vockley, J., … Wood, P. A. (1998). Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation. Proc Natl Acad Sci U S A, 95(26), 15592–15597. https://doi.org/10.1073/pnas.95.26.15592
Kurtz, D. M., P. Rinaldo, W. J. Rhead, L. Tian, D. S. Millington, J. Vockley, D. A. Hamm, et al. “Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation.” Proc Natl Acad Sci U S A 95, no. 26 (December 22, 1998): 15592–97. https://doi.org/10.1073/pnas.95.26.15592.
Kurtz DM, Rinaldo P, Rhead WJ, Tian L, Millington DS, Vockley J, et al. Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15592–7.
Kurtz, D. M., et al. “Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation.” Proc Natl Acad Sci U S A, vol. 95, no. 26, Dec. 1998, pp. 15592–97. Pubmed, doi:10.1073/pnas.95.26.15592.
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. Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15592–15597.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.95.26.15592

ISSN

0027-8424

Publication Date

December 22, 1998

Volume

95

Issue

26

Start / End Page

15592 / 15597

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Muscle, Skeletal
  • Mitochondria, Liver
  • Mice, Knockout
  • Mice
  • Liver
  • Lipid Metabolism, Inborn Errors
  • Humans
  • Fatty Acids, Nonesterified
  • Disease Models, Animal