Medium-chain acyl-CoA dehydrogenase deficiency in gene-targeted mice

Ravi J. Tolwani, Doug A. Hamm, Liqun Tian, J. Daniel Sharer, Jerry Vockley, Piero Rinaldo, Dietrich Matern, Trenton R. Schoeb, Philip A. Wood

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mitochondrial fatty acid β-oxidation in humans. To better understand the pathogenesis of this disease, we developed a mouse model for MCAD deficiency (MCAD-/-) by gene targeting in embryonic stem (ES) cells. The MCAD-/- mice developed an organic aciduria and fatty liver, and showed profound cold intolerance at 4 °C with prior fasting. The sporadic cardiac lesions seen in MCAD-/- mice have not been reported in human MCAD patients. There was significant neonatal mortality of MCAD -/- pups demonstrating similarities to patterns of clinical episodes and mortality in MCAD-deficient patients. The MCAD-deficient mouse reproduced important aspects of human MCAD deficiency and is a valuable model for further analysis of the roles of fatty acid oxidation and pathogenesis of human diseases involving fatty acid oxidation.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalPLoS genetics
Issue number2
StatePublished - 2005

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research


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