Adaptor protein Src-homology 2 domain containing E(SH2E)deficiency induces heart defect in zebrafish  

作　　者：Yu-lai Liang Yang-xi Hu Fang-fang Li Hong-min You Jian Chen Chun Liang Zhi-fu Guo Qing Jing 

机构地区：[1]Laboratory of Molecular Immunology,State Key Laboratory of Genetic Engineering,School of Life Sciences,Fudan University,Shanghai,200438,China [2]CAS Key Laboratory of Tissue Microenvironment and Tumor,Innovation Center for Intervention of Chronic Disease and Promotion of Health,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai,200031,China [3]Department of Cardiology,Second Affiliated Hospital of Naval Medical University,Shanghai,200003,China [4]Department of Pharmacy,Second Affiliated Hospital of Naval Medical University,Shanghai,200003,China [5]Department of Cardiology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200080,China [6]Department of Cardiovascular Medicine,Changhai Hospital,Naval Medical University,Shanghai,200433,China

出　　处：《Acta Pharmacologica Sinica》2025年第2期404-415,共12页中国药理学报(英文版)

基　　金：funded by the National Key Research and Development Program of China(2019YFA0802700);the National Natural Science Foundation of China(92168206,82400541);the Postdoctoral Fellowship Program of CPSF under Grant Number GZC20242284.

摘　　要：Adaptor proteins play crucial roles in signal transduction across diverse signaling pathways.Src-homology 2 domain-containing E(SH2E)is the adaptor protein highly expressed in vascular endothelial cells and myocardium during zebrafish embryogenesis.In this study we investigated the function and mechanisms of SH2E in cardiogenesis.We first analyzed the spatiotemporal expression of SH2E and then constructed zebrafish lines with SH2E deficiency using the CRISPR-Cas9 system.We showed that homozygous mutants developed progressive pericardial edema(PCE),dilated atrium,abnormal atrioventricular looping and thickened atrioventricular wall from 3 days post fertilization(dpf)until death;inducible overexpression of SH2E was able to partially rescue the PCE phenotype.Using transcriptome sequencing analysis,we demonstrated that the MAPK/ERK and NF-κB signaling pathways might be involved in SH2E-deficiency-caused PCE.This study underscores the pivotal role of SH2E in cardiogenesis,and might help to identify innovative diagnostic techniques and therapeutic strategies for congenital heart disease.

关 键 词：cardiac development pericardial edema Src-homology 2 domain containing E CRISPR/Cas9 ZEBRAFISH 

分 类 号：Q78[生物学—分子生物学]