• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

通过心肌细胞特异性条件性敲除Arhgef18建立心肌病模型并进行功能研究。

Establishment and functional studies of a model of cardiomyopathy with cardiomyocyte-specific conditional knockout of Arhgef18.

作者信息

Fu Xiaoqiong, Yuan Wenjing, Li Jiajin, Wan Kun, Ge Mei, Pan Bo, Lu Tiewei

机构信息

Department of Cardiology, Children's Hospital of Chongqing Medical University, National Clinical Key Cardiovascular Specialty, National Clinical Research Center for Child Health and Disorders, Key Laboratory of Children's Important Organ Development and Diseases of Chongqing Municipal Health Commission, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Key Laboratory of Pediatrics, ChongQing 400014, China.

Chongqing General Hospital, Chongqing University, Chongqing 400014, China.

出版信息

Dis Model Mech. 2025 Mar 1;18(3). doi: 10.1242/dmm.052172. Epub 2025 Mar 31.

DOI:10.1242/dmm.052172
PMID:40159883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11992352/
Abstract

The rising incidence of cardiomyopathies poses a significant threat to the physical and mental health of patients. The establishment of an animal model that accurately reflects the clinicopathological characteristics of cardiomyopathy is essential for investigating its pathogenesis. In this study, a cardiomyocyte-specific Arhgef18 conditional knockout (cKO) mouse model was established with Cre/LoxP technology, and the results confirmed that the protein encoded by Arhgef18 (Rho/Rac guanine nucleotide exchange factor 18) was knocked out effectively in the myocardium of Arhgef18flox/flox; Nkx2.5-Cre (Arhgef18fl/fl cKO) mice. Compared to Arhgef18fl/fl mice, Arhgef18fl/fl cKO mice presented with slower body weight growth and no differences in survival curves. Cardiac structure and function revealed that Arhgef18fl/fl cKO mice developed biventricular enlargement, ventricular wall thinning and left-ventricular systolic dysfunction, along with increased Nppa and Nppb mRNA expression levels. Additionally, Arhgef18fl/fl cKO mice showed cardiomyocyte cytoskeletal rearrangements and cell polarity disorders. Our study results suggest that Arhgef18 cKO mice could provide an ideal animal model for the genetic investigation of cardiomyopathy.

摘要

心肌病发病率的上升对患者的身心健康构成了重大威胁。建立能够准确反映心肌病临床病理特征的动物模型对于研究其发病机制至关重要。在本研究中，利用Cre/LoxP技术建立了心肌细胞特异性Arhgef18条件性敲除（cKO）小鼠模型，结果证实Arhgef18（Rho/Rac鸟嘌呤核苷酸交换因子18）编码的蛋白在Arhgef18flox/flox; Nkx2.5-Cre（Arhgef18fl/fl cKO）小鼠的心肌中被有效敲除。与Arhgef18fl/fl小鼠相比，Arhgef18fl/fl cKO小鼠体重增长较慢，生存曲线无差异。心脏结构和功能显示，Arhgef18fl/fl cKO小鼠出现双心室扩大、心室壁变薄和左心室收缩功能障碍，同时Nppa和Nppb mRNA表达水平升高。此外，Arhgef18fl/fl cKO小鼠表现出心肌细胞细胞骨架重排和细胞极性紊乱。我们的研究结果表明，Arhgef18 cKO小鼠可为心肌病的遗传学研究提供理想的动物模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cc/11992352/e806b8ab2e05/dmm-18-052172-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cc/11992352/71acb920c8ce/dmm-18-052172-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cc/11992352/8741951b2f23/dmm-18-052172-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cc/11992352/545106e85d65/dmm-18-052172-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cc/11992352/e806b8ab2e05/dmm-18-052172-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cc/11992352/71acb920c8ce/dmm-18-052172-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cc/11992352/8741951b2f23/dmm-18-052172-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cc/11992352/545106e85d65/dmm-18-052172-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cc/11992352/e806b8ab2e05/dmm-18-052172-g4.jpg

相似文献

1
Establishment and functional studies of a model of cardiomyopathy with cardiomyocyte-specific conditional knockout of Arhgef18.通过心肌细胞特异性条件性敲除Arhgef18建立心肌病模型并进行功能研究。
Dis Model Mech. 2025 Mar 1;18(3). doi: 10.1242/dmm.052172. Epub 2025 Mar 31.
2
Targeted intestinal deletion of Rho guanine nucleotide exchange factor 7, βPIX, impairs enterocyte proliferation, villus maturation, and mucosal defenses in mice.靶向肠道 Rho 鸟苷酸交换因子 7（βPIX）缺失会损害小鼠肠上皮细胞增殖、绒毛成熟和黏膜防御。
Am J Physiol Gastrointest Liver Physiol. 2021 Apr 1;320(4):G627-G643. doi: 10.1152/ajpgi.00415.2020. Epub 2021 Feb 10.
3
CXCR4 Cardiac Specific Knockout Mice Develop a Progressive Cardiomyopathy.CXCR4 心脏特异性敲除小鼠会发展出进行性心肌病。
Int J Mol Sci. 2019 May 8;20(9):2267. doi: 10.3390/ijms20092267.
4
Loss of GATAD1 in cardiomyocyte does not cause cardiomyopathy in mice.心肌细胞中GATAD1的缺失不会导致小鼠患心肌病。
J Mol Histol. 2024 Dec 6;56(1):33. doi: 10.1007/s10735-024-10297-z.
5
Rapid and highly efficient inducible cardiac gene knockout in adult mice using AAV-mediated expression of Cre recombinase.利用 AAV 介导的 Cre 重组酶表达实现成年小鼠快速高效的诱导性心脏基因敲除。
Cardiovasc Res. 2014 Oct 1;104(1):15-23. doi: 10.1093/cvr/cvu174. Epub 2014 Jul 31.
6
Connexin defects underlie arrhythmogenic right ventricular cardiomyopathy in a novel mouse model.在一种新型小鼠模型中，连接蛋白缺陷是致心律失常性右室心肌病的基础。
Hum Mol Genet. 2014 Mar 1;23(5):1134-50. doi: 10.1093/hmg/ddt508. Epub 2013 Oct 9.
7
ArhGEF18 regulates RhoA-Rock2 signaling to maintain neuro-epithelial apico-basal polarity and proliferation.ArhGEF18 通过调控 RhoA-Rock2 信号通路维持神经上皮的顶底极性和增殖。
Development. 2013 Jul;140(13):2787-97. doi: 10.1242/dev.096487. Epub 2013 May 22.
8
ARHGEF18 is a flow-responsive exchange factor controlling endothelial tight junctions and vascular leakage.ARHGEF18是一种流量响应交换因子，可控制内皮紧密连接和血管渗漏。
Cell Rep. 2025 Mar 25;44(3):115288. doi: 10.1016/j.celrep.2025.115288. Epub 2025 Feb 19.
9
DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere assembly.DAAM1和DAAM2是心肌成熟和肌节组装共同所需的。
Dev Biol. 2015 Dec 1;408(1):126-39. doi: 10.1016/j.ydbio.2015.10.003. Epub 2015 Oct 23.
10
Knockout of Sorbin And SH3 Domain Containing 2 (Sorbs2) in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice.心肌细胞中 Sorbin 和 SH3 域包含 2 型（Sorbs2）的敲除导致小鼠扩张型心肌病。
J Am Heart Assoc. 2022 Jul 5;11(13):e025687. doi: 10.1161/JAHA.122.025687. Epub 2022 Jun 22.

本文引用的文献

1
Nrg1 Regulates Cardiomyocyte Migration and Cell Cycle in Ventricular Development.Nrg1 调控心室发育中心肌细胞的迁移和细胞周期。
Circ Res. 2023 Nov 10;133(11):927-943. doi: 10.1161/CIRCRESAHA.123.323321. Epub 2023 Oct 17.
2
Genetics of Dilated Cardiomyopathy.扩张型心肌病的遗传学。
Annu Rev Med. 2024 Jan 29;75:417-426. doi: 10.1146/annurev-med-052422-020535. Epub 2023 Oct 3.
3
MYH7 in cardiomyopathy and skeletal muscle myopathy.MYH7 在心肌病和骨骼肌肌病中的作用。
Mol Cell Biochem. 2024 Feb;479(2):393-417. doi: 10.1007/s11010-023-04735-x. Epub 2023 Apr 20.
4
A Review of Left Ventricular Non-compaction Cardiomyopathy (LVNC).左心室致密化不全心肌病（LVNC）综述
J Community Hosp Intern Med Perspect. 2022 Nov 7;12(6):51-63. doi: 10.55729/2000-9666.1120. eCollection 2022.
5
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations.肌动蛋白-微管细胞骨架相互作用通过 MRTF-A/SRF 信号传导促进由 LMNA 突变引起的扩张型心肌病。
Nat Commun. 2022 Dec 22;13(1):7886. doi: 10.1038/s41467-022-35639-x.
6
Natural History of MYH7-Related Dilated Cardiomyopathy.MYH7相关扩张型心肌病的自然病史。
J Am Coll Cardiol. 2022 Oct 11;80(15):1447-1461. doi: 10.1016/j.jacc.2022.07.023. Epub 2022 Aug 22.
7
Phosphoproteomic Analysis Reveals Downstream PKA Effectors of AKAP Cypher/ZASP in the Pathogenesis of Dilated Cardiomyopathy.磷酸化蛋白质组学分析揭示了锚定蛋白Cypher/ZASP的下游蛋白激酶A效应因子在扩张型心肌病发病机制中的作用
Front Cardiovasc Med. 2021 Dec 13;8:753072. doi: 10.3389/fcvm.2021.753072. eCollection 2021.
8
Genotype and Cardiac Outcomes in Pediatric Dilated Cardiomyopathy.基因型与儿科扩张型心肌病的心脏结局。
J Am Heart Assoc. 2022 Jan 4;11(1):e022854. doi: 10.1161/JAHA.121.022854. Epub 2021 Dec 22.
9
PRDM16 Is a Compact Myocardium-Enriched Transcription Factor Required to Maintain Compact Myocardial Cardiomyocyte Identity in Left Ventricle.PRDM16 是一种紧凑的心肌细胞丰富的转录因子，对于维持左心室紧凑型心肌细胞特征至关重要。
Circulation. 2022 Feb 22;145(8):586-602. doi: 10.1161/CIRCULATIONAHA.121.056666. Epub 2021 Dec 17.
10
Generation and characterization of a Myh6-driven Cre knockin mouse line.生成和鉴定 Myh6 驱动型 Cre 敲入小鼠品系。
Transgenic Res. 2021 Dec;30(6):821-835. doi: 10.1007/s11248-021-00285-4. Epub 2021 Sep 20.