Mice deleted for heart-type cytochrome c oxidase subunit 7a1 develop dilated cardiomyopathy

Maik Hüttemann; Scott Klewer; Icksoo Lee; Alena Pecinova; Petr Pecina; Jenney Liu; Michael Lee; Jeffrey W. Doan; Douglas F Larson; Elise Slack; Bita Maghsoodi; Robert P. Erickson; Lawrence I. Grossman

doi:10.1016/j.mito.2011.11.002

Mice deleted for heart-type cytochrome c oxidase subunit 7a1 develop dilated cardiomyopathy

Maik Hüttemann, Scott Klewer, Icksoo Lee, Alena Pecinova, Petr Pecina, Jenney Liu, Michael Lee, Jeffrey W. Doan, Douglas F Larson, Elise Slack, Bita Maghsoodi, Robert P. Erickson, Lawrence I. Grossman

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34 Scopus citations

Abstract

Subunit 7a of mouse cytochrome c oxidase (Cox) displays a contractile muscle-specific isoform, Cox7a1, that is the major cardiac form. To gain insight into the role of this isoform, we have produced a new knockout mouse line that lacks Cox7a1. We show that homozygous and heterozygous Cox7a1 knockout mice, although viable, have reduced Cox activity and develop a dilated cardiomyopathy at 6. weeks of age. Surprisingly, the cardiomyopathy improves and stabilizes by 6. months of age. Cox7a1 knockout mice incorporate more of the "liver-type" isoform Cox7a2 into the cardiac Cox holoenzyme and, also surprisingly, have higher tissue ATP levels.

Original language	English (US)
Pages (from-to)	294-304
Number of pages	11
Journal	Mitochondrion
Volume	12
Issue number	2
DOIs	https://doi.org/10.1016/j.mito.2011.11.002
State	Published - Mar 2012

Keywords

Dilated cardiomyopathy
Electron transport chain
Gene knockout
Mitochondria
Oxidative phosphorylation

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Cell Biology

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10.1016/j.mito.2011.11.002

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title = "Mice deleted for heart-type cytochrome c oxidase subunit 7a1 develop dilated cardiomyopathy",

abstract = "Subunit 7a of mouse cytochrome c oxidase (Cox) displays a contractile muscle-specific isoform, Cox7a1, that is the major cardiac form. To gain insight into the role of this isoform, we have produced a new knockout mouse line that lacks Cox7a1. We show that homozygous and heterozygous Cox7a1 knockout mice, although viable, have reduced Cox activity and develop a dilated cardiomyopathy at 6. weeks of age. Surprisingly, the cardiomyopathy improves and stabilizes by 6. months of age. Cox7a1 knockout mice incorporate more of the {"}liver-type{"} isoform Cox7a2 into the cardiac Cox holoenzyme and, also surprisingly, have higher tissue ATP levels.",

keywords = "Dilated cardiomyopathy, Electron transport chain, Gene knockout, Mitochondria, Oxidative phosphorylation",

author = "Maik H{\"u}ttemann and Scott Klewer and Icksoo Lee and Alena Pecinova and Petr Pecina and Jenney Liu and Michael Lee and Doan, {Jeffrey W.} and Larson, {Douglas F} and Elise Slack and Bita Maghsoodi and Erickson, {Robert P.} and Grossman, {Lawrence I.}",

note = "Funding Information: This work was supported by a grant supplement from the National Institutes of Health (GM48517; LIG), the Center for Molecular Medicine and Genetics, Wayne State University, Detroit (MH), and a grant from the National Institutes of Health (GM089900; MH). ",

year = "2012",

month = mar,

doi = "10.1016/j.mito.2011.11.002",

language = "English (US)",

volume = "12",

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AU - Hüttemann, Maik

AU - Klewer, Scott

AU - Lee, Icksoo

AU - Pecinova, Alena

AU - Pecina, Petr

AU - Liu, Jenney

AU - Lee, Michael

AU - Doan, Jeffrey W.

AU - Larson, Douglas F

AU - Slack, Elise

AU - Maghsoodi, Bita

AU - Erickson, Robert P.

AU - Grossman, Lawrence I.

N1 - Funding Information: This work was supported by a grant supplement from the National Institutes of Health (GM48517; LIG), the Center for Molecular Medicine and Genetics, Wayne State University, Detroit (MH), and a grant from the National Institutes of Health (GM089900; MH).

PY - 2012/3

Y1 - 2012/3

N2 - Subunit 7a of mouse cytochrome c oxidase (Cox) displays a contractile muscle-specific isoform, Cox7a1, that is the major cardiac form. To gain insight into the role of this isoform, we have produced a new knockout mouse line that lacks Cox7a1. We show that homozygous and heterozygous Cox7a1 knockout mice, although viable, have reduced Cox activity and develop a dilated cardiomyopathy at 6. weeks of age. Surprisingly, the cardiomyopathy improves and stabilizes by 6. months of age. Cox7a1 knockout mice incorporate more of the "liver-type" isoform Cox7a2 into the cardiac Cox holoenzyme and, also surprisingly, have higher tissue ATP levels.

AB - Subunit 7a of mouse cytochrome c oxidase (Cox) displays a contractile muscle-specific isoform, Cox7a1, that is the major cardiac form. To gain insight into the role of this isoform, we have produced a new knockout mouse line that lacks Cox7a1. We show that homozygous and heterozygous Cox7a1 knockout mice, although viable, have reduced Cox activity and develop a dilated cardiomyopathy at 6. weeks of age. Surprisingly, the cardiomyopathy improves and stabilizes by 6. months of age. Cox7a1 knockout mice incorporate more of the "liver-type" isoform Cox7a2 into the cardiac Cox holoenzyme and, also surprisingly, have higher tissue ATP levels.

KW - Dilated cardiomyopathy

KW - Electron transport chain

KW - Gene knockout

KW - Mitochondria

KW - Oxidative phosphorylation

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JF - Mitochondrion

SN - 1567-7249

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ER -

Mice deleted for heart-type cytochrome c oxidase subunit 7a1 develop dilated cardiomyopathy

Abstract

Keywords

ASJC Scopus subject areas

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