Abstract：
:Mutations in the CFTR gene cause cystic fibrosis (CF) with myocardial dysfunction. However, it remains unknown whether CF-related heart disease is a secondary effect of pulmonary disease, or an intrinsic primary defect in the heart. Here, we used zebrafish, which lack lung tissue, to investigate the role of CFTR in cardiogenesis. Our findings demonstrated that the loss of CFTR impairs cardiac development from the cardiac progenitor stage, resulting in cardiac looping defects, a dilated atrium, pericardial edema, and a decrease in heart rate. Furthermore, we found that cardiac development was perturbed in wild-type embryos treated with a gating-specific CFTR channel inhibitor, CFTRinh-172, at the blastula stage of development, but not at later stages. Gene expression analysis of blastulas indicated that transcript levels, including mRNAs associated with cardiovascular diseases, were significantly altered in embryos derived from cftr mutants relative to controls. To evaluate the role of CFTR in human heart failure, we performed a genetic association study on individuals with dilated cardiomyopathy and found that the I556V mutation in CFTR, which causes a channel defect, was associated with the disease. Similar to other well-studied channel-defective CFTR mutants, CFTR I556V mRNA failed to restore cardiac dysplasia in mutant embryos. The present study revealed an important role for the CFTR ion channel in regulating cardiac development during early embryogenesis, supporting the hypothesis that CF-related heart disease results from an intrinsic primary defect in the heart.
journal_name
Mech Devjournal_title
Mechanisms of developmentauthors
Liu Y,Lin Z,Liu M,Liao H,Chen Y,Zhang X,Chan HC,Zhou B,Rao L,Sun Hdoi
10.1016/j.mod.2020.103627subject
Has Abstractpub_date
2020-09-01 00:00:00pages
103627eissn
0925-4773issn
1872-6356pii
S0925-4773(20)30032-0journal_volume
163pub_type
杂志文章abstract：:Unlike gap genes in the trunk region of Drosophila embryos, gap genes in the head were presumed not to regulate each other's transcription. Here, we show that in tailless (tll) loss-of-function mutants the empty spiracles (ems) expression domain in the head expands, whereas it retracts in tll gain-of-function embryos....
journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
pub_type： 杂志文章,评审
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
pub_type： 杂志文章
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journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2013.02.003
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
pub_type： 杂志文章
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journal_title：Mechanisms of development
pub_type： 杂志文章
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journal_title：Mechanisms of development
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doi：10.1016/s0925-4773(01)00471-3
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
pub_type： 杂志文章,评审
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
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journal_title：Mechanisms of development
pub_type： 杂志文章
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更新日期：2007-11-01 00:00:00
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journal_title：Mechanisms of development
pub_type： 杂志文章
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更新日期：2010-09-01 00:00:00
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journal_title：Mechanisms of development
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