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Gene Knock-Outs of Inositol 1,4,5-Trisphosphate Receptors Types 1 and 2 Result in Perturbation of Cardiogenesis

BACKGROUND: Inositol 1,4,5-trisphosphate receptors (IP(3)R1, 2, and 3) are intracellular Ca(2+) release channels that regulate various vital processes. Although the ryanodine receptor type 2, another type of intracellular Ca(2+) release channel, has been shown to play a role in embryonic cardiomyocy...

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Autores principales: Uchida, Keiko, Aramaki, Megumi, Nakazawa, Maki, Yamagishi, Chihiro, Makino, Shinji, Fukuda, Keiichi, Nakamura, Takeshi, Takahashi, Takao, Mikoshiba, Katsuhiko, Yamagishi, Hiroyuki
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931702/
https://www.ncbi.nlm.nih.gov/pubmed/20824138
http://dx.doi.org/10.1371/journal.pone.0012500
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author Uchida, Keiko
Aramaki, Megumi
Nakazawa, Maki
Yamagishi, Chihiro
Makino, Shinji
Fukuda, Keiichi
Nakamura, Takeshi
Takahashi, Takao
Mikoshiba, Katsuhiko
Yamagishi, Hiroyuki
author_facet Uchida, Keiko
Aramaki, Megumi
Nakazawa, Maki
Yamagishi, Chihiro
Makino, Shinji
Fukuda, Keiichi
Nakamura, Takeshi
Takahashi, Takao
Mikoshiba, Katsuhiko
Yamagishi, Hiroyuki
author_sort Uchida, Keiko
collection PubMed
description BACKGROUND: Inositol 1,4,5-trisphosphate receptors (IP(3)R1, 2, and 3) are intracellular Ca(2+) release channels that regulate various vital processes. Although the ryanodine receptor type 2, another type of intracellular Ca(2+) release channel, has been shown to play a role in embryonic cardiomyocytes, the functions of the IP(3)Rs in cardiogenesis remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: We found that IP(3)R1(−/−)-IP(3)R2(−/−) 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 IP(3)R1(−/−) or IP(3)R2(−/−) single-mutant mice at this developmental stage. The double-mutant 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 IP(3)R1/R2 and pharmacologic inhibition of IP(3)Rs 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 IP(3)Rs in cardiogenesis in part through the regulation of calcineurin-NFAT signaling.
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spelling pubmed-29317022010-09-03 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 PLoS One Research Article BACKGROUND: Inositol 1,4,5-trisphosphate receptors (IP(3)R1, 2, and 3) are intracellular Ca(2+) release channels that regulate various vital processes. Although the ryanodine receptor type 2, another type of intracellular Ca(2+) release channel, has been shown to play a role in embryonic cardiomyocytes, the functions of the IP(3)Rs in cardiogenesis remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: We found that IP(3)R1(−/−)-IP(3)R2(−/−) 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 IP(3)R1(−/−) or IP(3)R2(−/−) single-mutant mice at this developmental stage. The double-mutant 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 IP(3)R1/R2 and pharmacologic inhibition of IP(3)Rs 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 IP(3)Rs in cardiogenesis in part through the regulation of calcineurin-NFAT signaling. Public Library of Science 2010-09-01 /pmc/articles/PMC2931702/ /pubmed/20824138 http://dx.doi.org/10.1371/journal.pone.0012500 Text en Uchida et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
title Gene Knock-Outs of Inositol 1,4,5-Trisphosphate Receptors Types 1 and 2 Result in Perturbation of Cardiogenesis
title_full Gene Knock-Outs of Inositol 1,4,5-Trisphosphate Receptors Types 1 and 2 Result in Perturbation of Cardiogenesis
title_fullStr Gene Knock-Outs of Inositol 1,4,5-Trisphosphate Receptors Types 1 and 2 Result in Perturbation of Cardiogenesis
title_full_unstemmed Gene Knock-Outs of Inositol 1,4,5-Trisphosphate Receptors Types 1 and 2 Result in Perturbation of Cardiogenesis
title_short Gene Knock-Outs of Inositol 1,4,5-Trisphosphate Receptors Types 1 and 2 Result in Perturbation of Cardiogenesis
title_sort gene knock-outs of inositol 1,4,5-trisphosphate receptors types 1 and 2 result in perturbation of cardiogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931702/
https://www.ncbi.nlm.nih.gov/pubmed/20824138
http://dx.doi.org/10.1371/journal.pone.0012500
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