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Characterization of Ca(V)1.2 exon 33 heterozygous knockout mice and negative correlation between Rbfox1 and Ca(V)1.2 exon 33 expressions in human heart failure
Recently, we reported that homozygous deletion of alternative exon 33 of Ca(V)1.2 calcium channel in the mouse resulted in ventricular arrhythmias arising from increased Ca(V)1.2(Δ33) I(CaL) current density in the cardiomyocytes. We wondered whether heterozygous deletion of exon 33 might produce car...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774182/ https://www.ncbi.nlm.nih.gov/pubmed/28949795 http://dx.doi.org/10.1080/19336950.2017.1381805 |
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author | Wang, Juejin Li, Guang Yu, Dejie Wong, Yuk Peng Yong, Tan Fong Liang, Mui Cheng Liao, Ping Foo, Roger Hoppe, Uta C. Soong, Tuck Wah |
author_facet | Wang, Juejin Li, Guang Yu, Dejie Wong, Yuk Peng Yong, Tan Fong Liang, Mui Cheng Liao, Ping Foo, Roger Hoppe, Uta C. Soong, Tuck Wah |
author_sort | Wang, Juejin |
collection | PubMed |
description | Recently, we reported that homozygous deletion of alternative exon 33 of Ca(V)1.2 calcium channel in the mouse resulted in ventricular arrhythmias arising from increased Ca(V)1.2(Δ33) I(CaL) current density in the cardiomyocytes. We wondered whether heterozygous deletion of exon 33 might produce cardiac phenotype in a dose-dependent manner, and whether the expression levels of RNA splicing factors known to regulate alternative splicing of exon 33 might change in human heart failure. Unexpectedly, we found that exon 33(+/−) cardiomyocytes showed similar Ca(V)1.2 channel properties as wild-type cardiomyocyte, even though Ca(V)1.2(Δ33) channels exhibit a gain-in-function. In human hearts, we found that the mRNA level of splicing factor Rbfox1, but not Rbfox2, was downregulated in dilated cardiomyopathy, and CACNA1C mRNA level was dramatically decreased in the both of dilated and ischemic cardiomyopathy. These data imply Rbfox1 may be involved in the development of cardiomyopathies via regulating the alternative splicing of Ca(V)1.2 exon 33. (149 words) |
format | Online Article Text |
id | pubmed-5774182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-57741822018-01-30 Characterization of Ca(V)1.2 exon 33 heterozygous knockout mice and negative correlation between Rbfox1 and Ca(V)1.2 exon 33 expressions in human heart failure Wang, Juejin Li, Guang Yu, Dejie Wong, Yuk Peng Yong, Tan Fong Liang, Mui Cheng Liao, Ping Foo, Roger Hoppe, Uta C. Soong, Tuck Wah Channels (Austin) Addendum Recently, we reported that homozygous deletion of alternative exon 33 of Ca(V)1.2 calcium channel in the mouse resulted in ventricular arrhythmias arising from increased Ca(V)1.2(Δ33) I(CaL) current density in the cardiomyocytes. We wondered whether heterozygous deletion of exon 33 might produce cardiac phenotype in a dose-dependent manner, and whether the expression levels of RNA splicing factors known to regulate alternative splicing of exon 33 might change in human heart failure. Unexpectedly, we found that exon 33(+/−) cardiomyocytes showed similar Ca(V)1.2 channel properties as wild-type cardiomyocyte, even though Ca(V)1.2(Δ33) channels exhibit a gain-in-function. In human hearts, we found that the mRNA level of splicing factor Rbfox1, but not Rbfox2, was downregulated in dilated cardiomyopathy, and CACNA1C mRNA level was dramatically decreased in the both of dilated and ischemic cardiomyopathy. These data imply Rbfox1 may be involved in the development of cardiomyopathies via regulating the alternative splicing of Ca(V)1.2 exon 33. (149 words) Taylor & Francis 2017-09-26 /pmc/articles/PMC5774182/ /pubmed/28949795 http://dx.doi.org/10.1080/19336950.2017.1381805 Text en © 2018 The Author(s). Published with license by Taylor & Francis http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Addendum Wang, Juejin Li, Guang Yu, Dejie Wong, Yuk Peng Yong, Tan Fong Liang, Mui Cheng Liao, Ping Foo, Roger Hoppe, Uta C. Soong, Tuck Wah Characterization of Ca(V)1.2 exon 33 heterozygous knockout mice and negative correlation between Rbfox1 and Ca(V)1.2 exon 33 expressions in human heart failure |
title | Characterization of Ca(V)1.2 exon 33 heterozygous knockout mice and negative correlation between Rbfox1 and Ca(V)1.2 exon 33 expressions in human heart failure |
title_full | Characterization of Ca(V)1.2 exon 33 heterozygous knockout mice and negative correlation between Rbfox1 and Ca(V)1.2 exon 33 expressions in human heart failure |
title_fullStr | Characterization of Ca(V)1.2 exon 33 heterozygous knockout mice and negative correlation between Rbfox1 and Ca(V)1.2 exon 33 expressions in human heart failure |
title_full_unstemmed | Characterization of Ca(V)1.2 exon 33 heterozygous knockout mice and negative correlation between Rbfox1 and Ca(V)1.2 exon 33 expressions in human heart failure |
title_short | Characterization of Ca(V)1.2 exon 33 heterozygous knockout mice and negative correlation between Rbfox1 and Ca(V)1.2 exon 33 expressions in human heart failure |
title_sort | characterization of ca(v)1.2 exon 33 heterozygous knockout mice and negative correlation between rbfox1 and ca(v)1.2 exon 33 expressions in human heart failure |
topic | Addendum |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774182/ https://www.ncbi.nlm.nih.gov/pubmed/28949795 http://dx.doi.org/10.1080/19336950.2017.1381805 |
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