Medium-chain Acyl-CoA Dehydrogenase Deficiency in Gene-targeted Mice

Overview

Journal PLoS Genet

Specialty Genetics

Date 2005 Aug 27

PMID 16121256

Citations 65

Authors

Ravi J Tolwani

Doug A Hamm

Liqun Tian

J Daniel Sharer

Jerry Vockley

Piero Rinaldo

Dietrich Matern

Trenton R Schoeb

Philip A Wood

Affiliations

Soon will be listed here.

Abstract

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.

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