Overexpressing dominant negative MyD88 induces cardiac dysfunction in transgenic mice

Wei Qian Chen, Chuan Fu Li, Xuan Jiang, Hai Bin Ruan, Xin Qi, Li Liu, Qing Shun Zhao, Xiang Gao

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Myeloid differentiation protein-88 (MyD88) is a crucial adaptor protein in the innate immune response. A protective role for MyD88 in normal cardiac function has been proposed in a surgical hypertrophic model. To assess the in vivo role of MyD88 in cardiac remodeling, we generated transgenic mice with cardiac-restricted expression of a dominant negative mutant of MyD88 (dnMyD88). Surprisingly, dnMyD88 transgenic mice displayed characteristic features of heart failure; including heart weight increase, cardiomyocytes enlargement, interstitial fibrosis, and re-expression of "fetal" genes. Echocardiographic examination of dnMyD88 hearts revealed dilated chamber volume and reduced cardiac contractility. DnMyD88 mice died from heart failure before they were 7 months old, as shown by Kaplan-Meier analysis. Additionally, the heart failure phenotype of dnMyD88 mice was associated with abnormal activation of the Akt/GSK-3β signaling pathway. These data provide the first evidence that normal MyD88 signaling is crucial for maintaining the physiological function of the adult heart.

Original languageEnglish (US)
Pages (from-to)3569-3575
Number of pages7
JournalChinese Science Bulletin
Issue number31
StatePublished - Nov 2010

Bibliographical note

Funding Information:
The authors would like to thank Jean Philippe York for helpful language editing of the manuscript; Xiaowei Ma, Jizheng Ma, Shushu Zhu, Yihong Zhong and Xiaomei Ge for technological supports. This work was supported in part by the National Natural Science Foundation of China (30825024), the Ministry of Science and Technology of China (2006BAI23B00, 2005CB522501 and 2006CB943500).

Copyright 2011 Elsevier B.V., All rights reserved.


  • Akt
  • GSK-3
  • MyD88
  • cardiac dysfunction
  • dilated cardiomyopathy


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