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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1315-1322
Number of pages8
JournalCell Death and Differentiation
Volume16
Issue number10
DOIs
Publication statusPublished - Jun 9 2009

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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

Cite this

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.

In: Cell Death and Differentiation, Vol. 16, No. 10, 09.06.2009, p. 1315-1322.

Research output: Contribution to journalArticle

Behmanesh M, Sakumi K, Abolhassani N, Toyokuni S, Oka S, Ohnishi YN et al. ITPase-deficient mice show growth retardation and die before weaning. Cell Death and Differentiation. 2009 Jun 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. In: Cell Death and Differentiation. 2009 ; Vol. 16, No. 10. pp. 1315-1322.
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