Wu Calvin, Sharma Kanishk, Laster Kyle, Hersi Mohamed, Torres Christina, Lukas Thomas J, Moore Ernest J
Department of Molecular Pharmacology & Biological Chemistry, Northwestern University, Chicago, IL 60611, USA.
BMC Physiol. 2014 Feb 20;14:1. doi: 10.1186/1472-6793-14-1.
KCNQx genes encode slowly activating-inactivating K+ channels, are linked to physiological signal transduction pathways, and mutations in them underlie diseases such as long QT syndrome (KCNQ1), epilepsy in adults (KCNQ2/3), benign familial neonatal convulsions in children (KCNQ3), and hearing loss or tinnitus in humans (KCNQ4, but not KCNQ5). Identification of kcnqx potassium channel transcripts in zebrafish (Danio rerio) remains to be fully characterized although some genes have been mapped to the genome. Using zebrafish genome resources as the source of putative kcnq sequences, we investigated the expression of kcnq1-5 in heart, brain and ear tissues.
Overall expression of the kcnqx channel transcripts is similar to that found in mammals. We found that kcnq1 expression was highest in the heart, and also present in the ear and brain. kcnq2 was lowest in the heart, while kcnq3 was highly expressed in the brain, heart and ear. kcnq5 expression was highest in the ear. We analyzed zebrafish genomic clones containing putative kcnq4 sequences to identify transcripts and protein for this highly conserved member of the Kcnq channel family. The zebrafish appears to have two kcnq4 genes that produce distinct mRNA species in brain, ear, and heart tissues.
We conclude that the zebrafish is an attractive model for the study of the KCNQ (Kv7) superfamily of genes, and are important to processes involved in neuronal excitability, cardiac anomalies, epileptic seizures, and hearing loss or tinnitus.
KCNQx基因编码缓慢激活 - 失活的钾通道,与生理信号转导途径相关,其突变是诸如长QT综合征(KCNQ1)、成人癫痫(KCNQ2/3)、儿童良性家族性新生儿惊厥(KCNQ3)以及人类听力丧失或耳鸣(KCNQ4,但不包括KCNQ5)等疾病的基础。尽管一些基因已被定位到斑马鱼(Danio rerio)基因组中,但斑马鱼中kcnqx钾通道转录本的鉴定仍有待充分表征。利用斑马鱼基因组资源作为假定kcnq序列的来源,我们研究了kcnq1 - 5在心脏、大脑和耳朵组织中的表达。
kcnqx通道转录本的总体表达与在哺乳动物中发现的相似。我们发现kcnq1在心脏中表达最高,在耳朵和大脑中也有表达。kcnq2在心脏中表达最低,而kcnq3在大脑、心脏和耳朵中高表达。kcnq5在耳朵中表达最高。我们分析了包含假定kcnq4序列的斑马鱼基因组克隆,以鉴定该Kcnq通道家族高度保守成员的转录本和蛋白质。斑马鱼似乎有两个kcnq4基因,它们在大脑、耳朵和心脏组织中产生不同的mRNA种类。
我们得出结论,斑马鱼是研究KCNQ(Kv7)基因超家族的有吸引力的模型,并且对涉及神经元兴奋性、心脏异常、癫痫发作以及听力丧失或耳鸣的过程很重要。