Overexpressing Dominant Negative MyD88 Induces Cardiac Dysfunction in Transgenic Mice
Document Type
Article
Publication Date
11-1-2010
Description
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.
Citation Information
Chen, Wei Q.; Li, Chuan Fu; Jiang, Xuan; Ruan, Hai B.; Qi, Xin; Liu, Li; Zhao, Qing S.; and Gao, Xiang. 2010. Overexpressing Dominant Negative MyD88 Induces Cardiac Dysfunction in Transgenic Mice. Chinese Science Bulletin. Vol.55(31). 3569-3575. https://doi.org/10.1007/s11434-010-4080-9 ISSN: 1001-6538