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Chinese Science Bulletin

, Volume 55, Issue 31, pp 3569–3575 | Cite as

Overexpressing dominant negative MyD88 induces cardiac dysfunction in transgenic mice

  • WeiQian Chen
  • ChuanFu Li
  • Xuan Jiang
  • HaiBin Ruan
  • Xin Qi
  • Li Liu
  • QingShun Zhao
  • Xiang Gao
Article Animal Genetics

Abstract

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.

Keywords

dilated cardiomyopathy cardiac dysfunction MyD88 Akt GSK-3 

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Copyright information

© Science China Press and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • WeiQian Chen
    • 1
  • ChuanFu Li
    • 1
    • 2
  • Xuan Jiang
    • 1
  • HaiBin Ruan
    • 1
  • Xin Qi
    • 1
  • Li Liu
    • 1
    • 3
  • QingShun Zhao
    • 1
  • Xiang Gao
    • 1
  1. 1.Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research CenterNanjing UniversityNanjingChina
  2. 2.Department of SurgeryEast Tennessee State UniversityJohnson CityUSA
  3. 3.Departments of Gerontology and CardiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

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