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

Academic Article

Abstract

  • 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.
  • Authors

    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