Transgenic analysis of the role of FKBP12.6 in cardiac function and intracellular calcium release

Ying Liu, Hanying Chen, Guangju Ji, Baiyan Li, Peter J. Mohler, Zhiming Zhu, Weidong Yong, Zhuang Chen, Xuehong Xu, Hongbo Xin, Weinian Shou

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

FK506 binding protein12.6 (FKBP12.6) binds to the Ca 2+ release channel ryanodine receptor (RyR2) in cardiomyocytes and stabilizes RyR2 to prevent premature sarcoplasmic reticulum Ca 2+ release. Previously, two different mouse strains deficient in FKBP12.6 were reported to have different abnormal cardiac phenotypes. The first mutant strain displayed sex-dependent cardiac hypertrophy, while the second displayed exercise-induced cardiac arrhythmia and sudden death. In this study, we tested whether FKBP12.6-deficient mice that display hypertrophic hearts can develop exercise-induced cardiac sudden death and whether the hypertrophic heart is a direct consequence of abnormal calcium handling in mutant cardiomyocytes. Our data show that FKBP12.6-deficient mice with cardiac hypertrophy do not display exercise-induced arrhythmia and/or sudden cardiac death. To investigate the role of FKBP12.6 overexpression for cardiac function and cardiomyocyte calcium release, we generated a transgenic mouse line with cardiac specific overexpression of FKBP12.6 using α-myosin heavy chain (αMHC) promoter. MHC-FKBP12.6 mice displayed normal cardiac development and function. We demonstrated that MHC-FKBP12.6 mice are able to rescue abnormal cardiac hypertrophy and abnormal calcium release in FKBP12.6-deficient mice.

Original languageEnglish
Pages (from-to)620-627
Number of pages8
JournalAssay and Drug Development Technologies
Volume9
Issue number6
DOIs
StatePublished - Dec 1 2011

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Tacrolimus
Calcium
Ryanodine Receptor Calcium Release Channel
Myosin Heavy Chains
Cardiomegaly
Cardiac Myocytes
Sudden Cardiac Death
Cardiac Arrhythmias
Sarcoplasmic Reticulum
Sudden Death
Transgenic Mice
Phenotype

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine

Cite this

Transgenic analysis of the role of FKBP12.6 in cardiac function and intracellular calcium release. / Liu, Ying; Chen, Hanying; Ji, Guangju; Li, Baiyan; Mohler, Peter J.; Zhu, Zhiming; Yong, Weidong; Chen, Zhuang; Xu, Xuehong; Xin, Hongbo; Shou, Weinian.

In: Assay and Drug Development Technologies, Vol. 9, No. 6, 01.12.2011, p. 620-627.

Research output: Contribution to journalArticle

Liu, Ying ; Chen, Hanying ; Ji, Guangju ; Li, Baiyan ; Mohler, Peter J. ; Zhu, Zhiming ; Yong, Weidong ; Chen, Zhuang ; Xu, Xuehong ; Xin, Hongbo ; Shou, Weinian. / Transgenic analysis of the role of FKBP12.6 in cardiac function and intracellular calcium release. In: Assay and Drug Development Technologies. 2011 ; Vol. 9, No. 6. pp. 620-627.
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