ITPase-deficient mice show growth retardation and die before weaning

M. Behmanesh, K. Sakumi, N. Abolhassani, S. Toyokuni, S. Oka, Y. N. Ohnishi, D. Tsuchimoto, Y. Nakabeppu

研究成果: ジャーナルへの寄稿記事

46 引用 (Scopus)

抄録

Inosine triphosphate pyrophosphatase (ITPase), the enzyme that hydrolyzes ITP and other deaminated purine nucleoside triphosphates to the corresponding purine nucleoside monophosphate and pyrophosphate, is encoded by the Itpa gene. In this study, we established Itpa knockout (KO) mice and used them to show that ITPase is required for the normal organization of sarcomeres in the heart. Itpa-/- mice died about 2 weeks after birth with features of growth retardation and cardiac myofiber disarray, similar to the phenotype of the cardiac α-actin KO mouse. Inosine nucleotides were found to accumulate in both the nucleotide pool and RNA of Itpa-/- mice. These data suggest that the role of ITPase in mice is to exclude ITP from the ATP pool, and the main target substrate of this enzyme is rITP. Our data also suggest that cardiomyopathy, which is mainly caused by mutations in sarcomeric protein-encoding genes, is also caused by a defect in maintaining the quality of the ATP pool, which is an essential requirement for sarcomere function.

元の言語英語
ページ(範囲)1315-1322
ページ数8
ジャーナルCell Death and Differentiation
16
発行部数10
DOI
出版物ステータス出版済み - 6 9 2009

Fingerprint

Inosine Triphosphate
Weaning
Pyrophosphatases
Purine Nucleosides
Sarcomeres
Growth
Knockout Mice
Inosine Nucleotides
Adenosine Triphosphate
Enzymes
Cardiomyopathies
Actins
Nucleotides
Parturition
RNA
Phenotype
Mutation
mouse ITPA protein
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

これを引用

ITPase-deficient mice show growth retardation and die before weaning. / Behmanesh, M.; Sakumi, K.; Abolhassani, N.; Toyokuni, S.; Oka, S.; Ohnishi, Y. N.; Tsuchimoto, D.; Nakabeppu, Y.

:: Cell Death and Differentiation, 巻 16, 番号 10, 09.06.2009, p. 1315-1322.

研究成果: ジャーナルへの寄稿記事

Behmanesh M, Sakumi K, Abolhassani N, Toyokuni S, Oka S, Ohnishi YN その他. ITPase-deficient mice show growth retardation and die before weaning. Cell Death and Differentiation. 2009 6 9;16(10):1315-1322. https://doi.org/10.1038/cdd.2009.53
Behmanesh, M. ; Sakumi, K. ; Abolhassani, N. ; Toyokuni, S. ; Oka, S. ; Ohnishi, Y. N. ; Tsuchimoto, D. ; Nakabeppu, Y. / ITPase-deficient mice show growth retardation and die before weaning. :: Cell Death and Differentiation. 2009 ; 巻 16, 番号 10. pp. 1315-1322.
@article{d188cf6ed93d451fb2d2911cb33193a0,
title = "ITPase-deficient mice show growth retardation and die before weaning",
abstract = "Inosine triphosphate pyrophosphatase (ITPase), the enzyme that hydrolyzes ITP and other deaminated purine nucleoside triphosphates to the corresponding purine nucleoside monophosphate and pyrophosphate, is encoded by the Itpa gene. In this study, we established Itpa knockout (KO) mice and used them to show that ITPase is required for the normal organization of sarcomeres in the heart. Itpa-/- mice died about 2 weeks after birth with features of growth retardation and cardiac myofiber disarray, similar to the phenotype of the cardiac α-actin KO mouse. Inosine nucleotides were found to accumulate in both the nucleotide pool and RNA of Itpa-/- mice. These data suggest that the role of ITPase in mice is to exclude ITP from the ATP pool, and the main target substrate of this enzyme is rITP. Our data also suggest that cardiomyopathy, which is mainly caused by mutations in sarcomeric protein-encoding genes, is also caused by a defect in maintaining the quality of the ATP pool, which is an essential requirement for sarcomere function.",
author = "M. Behmanesh and K. Sakumi and N. Abolhassani and S. Toyokuni and S. Oka and Ohnishi, {Y. N.} and D. Tsuchimoto and Y. Nakabeppu",
year = "2009",
month = "6",
day = "9",
doi = "10.1038/cdd.2009.53",
language = "English",
volume = "16",
pages = "1315--1322",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - ITPase-deficient mice show growth retardation and die before weaning

AU - Behmanesh, M.

AU - Sakumi, K.

AU - Abolhassani, N.

AU - Toyokuni, S.

AU - Oka, S.

AU - Ohnishi, Y. N.

AU - Tsuchimoto, D.

AU - Nakabeppu, Y.

PY - 2009/6/9

Y1 - 2009/6/9

N2 - Inosine triphosphate pyrophosphatase (ITPase), the enzyme that hydrolyzes ITP and other deaminated purine nucleoside triphosphates to the corresponding purine nucleoside monophosphate and pyrophosphate, is encoded by the Itpa gene. In this study, we established Itpa knockout (KO) mice and used them to show that ITPase is required for the normal organization of sarcomeres in the heart. Itpa-/- mice died about 2 weeks after birth with features of growth retardation and cardiac myofiber disarray, similar to the phenotype of the cardiac α-actin KO mouse. Inosine nucleotides were found to accumulate in both the nucleotide pool and RNA of Itpa-/- mice. These data suggest that the role of ITPase in mice is to exclude ITP from the ATP pool, and the main target substrate of this enzyme is rITP. Our data also suggest that cardiomyopathy, which is mainly caused by mutations in sarcomeric protein-encoding genes, is also caused by a defect in maintaining the quality of the ATP pool, which is an essential requirement for sarcomere function.

AB - Inosine triphosphate pyrophosphatase (ITPase), the enzyme that hydrolyzes ITP and other deaminated purine nucleoside triphosphates to the corresponding purine nucleoside monophosphate and pyrophosphate, is encoded by the Itpa gene. In this study, we established Itpa knockout (KO) mice and used them to show that ITPase is required for the normal organization of sarcomeres in the heart. Itpa-/- mice died about 2 weeks after birth with features of growth retardation and cardiac myofiber disarray, similar to the phenotype of the cardiac α-actin KO mouse. Inosine nucleotides were found to accumulate in both the nucleotide pool and RNA of Itpa-/- mice. These data suggest that the role of ITPase in mice is to exclude ITP from the ATP pool, and the main target substrate of this enzyme is rITP. Our data also suggest that cardiomyopathy, which is mainly caused by mutations in sarcomeric protein-encoding genes, is also caused by a defect in maintaining the quality of the ATP pool, which is an essential requirement for sarcomere function.

UR - http://www.scopus.com/inward/record.url?scp=70349174735&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349174735&partnerID=8YFLogxK

U2 - 10.1038/cdd.2009.53

DO - 10.1038/cdd.2009.53

M3 - Article

C2 - 19498443

AN - SCOPUS:70349174735

VL - 16

SP - 1315

EP - 1322

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 10

ER -