当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF CARDIOLOGY期刊下所有文献 > Identification of KIAA0196 as a novel susceptibility gene for myofibril structural disorganization in cardiac development.

Identification of KIAA0196 as a novel susceptibility gene for myofibril structural disorganization in cardiac development.

Abstract：

BACKGROUND:Congenital heart disease is one of the most common cardiac malformation-related diseases worldwide. Some causative genes have been identified but can explain only a small proportion of all cases; therefore, the discovery of novel susceptibility genes and/or modifier genes for abnormal cardiac development remains a major challenge. METHODS:We used a single nucleotide polymorphism (SNP) array, and next-generation sequencing (NGS) was conducted to screen and quickly identify candidate genes. KIAA0196 knockout zebrafish and mice were generated by CRISPR/Cas9 to detect whether or how KIAA0196 deficiency would influence cardiac development. RESULTS:Homozygous, but not heterozygous, zebrafish and mice showed early embryonic lethality. At the embryonic stage, microscopic examination and dissection revealed pericardial edema and ventricle enlargement in homozygous zebrafish and obviously delayed cardiac development in heterozygous mice, while echocardiography and tissue staining showed that significantly decreased cardiac function, ventricle enlargement, myofibril loss, and significantly reduced trabecular muscle density were observed in adult heterozygous zebrafish and mice. Most importantly, immunostaining and electron microscopy showed that there was a significant increase in sarcomere structural disorganization and myofibril structural integrity loss in KIAA0196 mutants. Furthermore, substantial downregulation in other sarcomeric genes and proteins was detected and verified in a mouse model via transcriptome and proteomics analyses; these changes especially affected the myosin heavy or light chain (MYH or MYL) family genes. CONCLUSION:We identified KIAA0196 for the first time as a susceptibility gene for abnormal cardiac development. KIAA0196 deficiency may cause abnormal heart development by influencing the structural integrity of myofibrils.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Bu H,Yang Y,Wu Q,Tan Z,Gong X,Hu S,Zhao T

doi

10.1016/j.ijcard.2020.05.029

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

81-88

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(20)30914-1

journal_volume

314

pub_type

杂志文章

在线工具

Identification of KIAA0196 as a novel susceptibility gene for myofibril structural disorganization in cardiac development.