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

doi:10.1371/journal.pgen.0010023

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

Laboratory Medicine and Pathology

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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.

Original language	English (US)
Pages (from-to)	205-212
Number of pages	8
Journal	PLoS genetics
Volume	1
Issue number	2
DOIs	https://doi.org/10.1371/journal.pgen.0010023
State	Published - 2005

ASJC Scopus subject areas

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

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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.",

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AU - Hamm, Doug A.

AU - Tian, Liqun

AU - Sharer, J. Daniel

AU - Vockley, Jerry

AU - Rinaldo, Piero

AU - Matern, Dietrich

AU - Schoeb, Trenton R.

AU - Wood, Philip A.

PY - 2005

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AB - 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.

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

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