Medium-chain acyl-CoA dehydrogenase deficiency in gene-targeted mice.
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mitochondrial fatty acid beta-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 degrees 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.
Tolwani
Ravi J
RJ
Department of Genetics, University of Alabama, Birmingham, Alabama, USA.
Hamm
Doug A
DA
Tian
Liqun
L
Sharer
J Daniel
JD
Vockley
Jerry
J
Rinaldo
Piero
P
Matern
Dietrich
D
Schoeb
Trenton R
TR
Wood
Philip A
PA
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency*; D000818:Animals; D003080:Cold Temperature; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000166:cytology; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver; D008052:Lipid Metabolism, Inborn Errors / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D013234:Stem Cells; D015996:Survival Rate
D005227:Fatty Acids; D042964:Acyl-CoA Dehydrogenase