Modeling long QT syndrome using gene-edited pigs
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1216026 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32133615_1.fastq.gz | Fastqsanger.gz | |||
| SRR32133615_2.fastq.gz | Fastqsanger.gz | |||
| SRR32133616_1.fastq.gz | Fastqsanger.gz | |||
| SRR32133616_2.fastq.gz | Fastqsanger.gz | |||
| SRR32133617_1.fastq.gz | Fastqsanger.gz |
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Project description:To date, KCNH2 mutations identified in LQT2 patients have been heavily studied by heterologous expression systems, allowing for pathogenicity evaluation of a certain hERG mutation by overexpressing mutant channels. However, they fall short in mimicking the full spectrum of electrophysiological changes and ion channel remodeling that occur in cardiomyocytes under physiological conditions in the context of LQT. Due to the marked differences in the lifespan, size, anatomy and physiology from humans, current zebrafish and rodent models cannot fully mimic the abnormal QT interval diseases 2. For instance, rodents exhibit an extremely higher heart rate and a much shorter action potential duration (APD) compared to humans. IKr is the predominant repolarizing current in human ventricles while inhibition of IKr in rodents has no significant effect on ventricular repolarization, making it infeasible to study LQT2 by genetic mouse model 3. Hence, there is a crucial need to construct an animal model capable of mimicking human inherited arrhythmia conditions. To address the above scientific question, we chose to create a miniature pig model. Given many physiological similarities with humans, and breeding and genome editing advantages (when compared to non-human primates), To explore the mechanism underlying mutation of KCNH2 caused LQT, we compared the transcriptomes of KCNH2-mut pigs and WT controls
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