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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...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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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. |
format | Text |
id | pubmed-2931702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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