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

Academic Article


  • 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. © 2005 Tolwani et al. -/- -/- -/- -/-
  • Published In

  • PLoS Genetics  Journal
  • Digital Object Identifier (doi)

    Author List

  • Tolwani RJ; Hamm DA; Tian L; Sharer JD; Vockley J; Rinaldo P; Matern D; Schoeb TR; Wood PA
  • Start Page

  • 0205
  • End Page

  • 0212
  • Volume

  • 1
  • Issue

  • 2