Phenomics of cardiac chloride channels.
Phenomics of cardiac chloride channels.
复制标题
DOI：
10.1002/cphy.c110014
复制
发表时间：
2013-04
影响因子：
5.8
通讯作者：
Duan DD
中科院分区：
文献类型：
--
作者：
Duan DD
正向遗传学研究已经在心脏中发现了几个氯(Cl-−)通道基因，包括cftr、clc-2、clc-3、clca、Bestrophin和ANO1。最近利用基因打靶和转基因技术研究心脏CL-−通道功能的反向遗传学研究表明，CI-−通道可能参与心律失常的发生、心肌肥大和心力衰竭，以及对缺血再灌注的心脏保护作用。然而，由于动物对靶向基因操作的代偿性改变，心脏Cl-−通道的生理或病理生理学表型的研究变得复杂。或者，通过限制代偿对表型的影响，组织特异性条件性或可诱导的基因敲除或敲除动物模型可能在特定的CL−通道的表型研究中更有价值。氯离子−通道的整合功能可能涉及氯离子−通道亚蛋白质组的多蛋白复合体。类似的表型可以从细胞网络中受遗传和环境因素影响的不同蛋白质通路中获得。表型组学方法将表型描述为一个完整的表型组，并在基因组/蛋白质组/表型组的范围内系统地研究引起特定表型的分子变化，可能提供更全面的了解心脏每个CL-−通道在健康和疾病背景下的完整功能。
Forward genetic studies have identified several chloride (Cl−) channel genes, including CFTR, ClC-2, ClC-3, CLCA, Bestrophin, and Ano1, in the heart. Recent reverse genetic studies using gene targeting and transgenic techniques to delineate the functional role of cardiac Cl− channels have shown that Cl− channels may contribute to cardiac arrhythmogenesis, myocardial hypertrophy and heart failure, and cardioprotection against ischemia reperfusion. The study of physiological or pathophysiological phenotypes of cardiac Cl− channels, however, is complicated by the compensatory changes in the animals in response to the targeted genetic manipulation. Alternatively, tissue-specific conditional or inducible knockout or knockin animal models may be more valuable in the phenotypic studies of specific Cl− channels by limiting the effect of compensation on the phenotype. The integrated function of Cl− channels may involve multiprotein complexes of the Cl− channel subproteome. Similar phenotypes can be attained from alternative protein pathways within cellular networks, which are influenced by genetic and environmental factors. The phenomics approach, which characterizes phenotypes as a whole phenome and systematically studies the molecular changes that give rise to particular phenotypes achieved by modifying the genotype under the scope of genome/proteome/phenome, may provide more complete understanding of the integrated function of each cardiac Cl− channel in the context of health and disease.
登录
查看更多内容
影响因子：
1.5
作者：
Bogue, MA;Grubb, SC
通讯作者：
Grubb, SC
DOI：
10.1085/jgp.200409040
发表时间：
2004-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Browe DM;Baumgarten CM
通讯作者：
Baumgarten CM
影响因子：
3.5
作者：
CID, LP;MONTROSERAFIZADEH, C;CUTTING, GR
通讯作者：
CUTTING, GR
影响因子：
4.8
作者：
Baker, MA;Lane, DJR;Lawen, A
通讯作者：
Lawen, A
影响因子：
4.8
作者：
Boujaoude, LC;Bradshaw-Wilder, C;Obeid, LM
通讯作者：
Obeid, LM