Gene knock-outs of inositol 1,4,5-trisphosphate receptors types 1 and 2 result in perturbation of cardiogenesis

Keiko Uchida, Megumi Aramaki, Maki Nakazawa, Chihiro Yamagishi, Shinji Makino, Keiichi Fukuda, Takeshi Nakamura, Takao Takahashi, Katsuhiko Mikoshiba, Hiroyuki Yamagishi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: Inositol 1,4,5-trisphosphate receptors (IP3R1, 2, and 3) are intracellular Ca2+ release channels that regulatevarious vital processes. Although the ryanodine receptor type 2, another type of intracellular Ca2+ release channel, has been shown to play a role in embryonic cardiomyocytes, the functions of the IP3Rs in cardiogenesis remain unclear. Methodology/Principal Findings: We found that IP3R1-/-IP3R22/2 double-mutant mice died in utero with developmental defects of the ventricular myocardium and atrioventricular (AV) canal of the heart by embryonic day (E) 11.5, even though no cardiac defect was detectable in IP3R12/2 or IP3R22/2 single-mutant mice at this developmental stage. The doublemutant phenotype resembled that of mice deficient for calcineurin/NFATc signaling, and NFATc was inactive in embryonic hearts from the double knockout-mutant mice. The double mutation of IP3R1/R2 and pharmacologic inhibition of IP3Rs mimicked the phenotype of the AV valve defect that result from the inhibition of calcineurin, and it could be rescued by constitutively active calcineurin. Conclusions/Significance: Our results suggest an essential role for IP3Rs in cardiogenesis in part through the regulation of calcineurin-NFAT signaling.

Original languageEnglish
Article numbere12500
Pages (from-to)1-10
Number of pages10
JournalPLoS One
Volume5
Issue number9
DOIs
Publication statusPublished - 2010

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Inositol 1,4,5-Trisphosphate Receptors
Calcineurin
Genes
receptors
mice
Defects
genes
heart
ryanodine receptors
Phenotype
calcium
phenotype
mutants
Ryanodine Receptor Calcium Release Channel
knockout mutants
Canals
myocardium
Cardiac Myocytes
Knockout Mice
Myocardium

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gene knock-outs of inositol 1,4,5-trisphosphate receptors types 1 and 2 result in perturbation of cardiogenesis. / Uchida, Keiko; Aramaki, Megumi; Nakazawa, Maki; Yamagishi, Chihiro; Makino, Shinji; Fukuda, Keiichi; Nakamura, Takeshi; Takahashi, Takao; Mikoshiba, Katsuhiko; Yamagishi, Hiroyuki.

In: PLoS One, Vol. 5, No. 9, e12500, 2010, p. 1-10.

Research output: Contribution to journalArticle

Uchida, Keiko ; Aramaki, Megumi ; Nakazawa, Maki ; Yamagishi, Chihiro ; Makino, Shinji ; Fukuda, Keiichi ; Nakamura, Takeshi ; Takahashi, Takao ; Mikoshiba, Katsuhiko ; Yamagishi, Hiroyuki. / Gene knock-outs of inositol 1,4,5-trisphosphate receptors types 1 and 2 result in perturbation of cardiogenesis. In: PLoS One. 2010 ; Vol. 5, No. 9. pp. 1-10.
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