title: Cardiomyocyte specific deletion of PP2A causes cardiac hypertrophy.
abstract: Cardiac hypertrophy is a common pathological alteration in heart disease, which has been reported to be connected with serine/threonine protein phosphatases that control the dephosphorylation of a variety of cardiac proteins. Herein, we generated protein phosphatase type 2A knockout expressing a tamoxifen-inducible Cre recombinase protein fused to two mutant estrogen-receptor ligand-binding domains (MerCreMer) under the control of the a-myosin heavy chain promoter. Cardiac function of mice was determined by echocardiography. Decrease in PP2A activity leads to increased cardiomyocyte hypertrophy and fibrosis. Loss of PP2ACα leads to the heart failure, including the changes of EF, FS, LV, ANP and BNP. On the molecular level, knockout mice shows increased expression of B55a and B56e at 60 days after tamoxifen injection. Additionally, the regulation of the Akt/GSK3β/β-catenin pathway is severely disturbed in knockout mice. In conclusion, cardiomyocyte specific deletion of PP2A gene causes the cardiac hypertrophy. We will use the knockout mice to generate a type of cardiomyocyte hypertrophy mouse model with myocardial fibrosis.
authors.affiliation: Department of Pharmacology, Basic Medical Sciences of Nanjing Medical University Nanjing 210029, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Basic Medical Sciences of Nanjing Medical University Nanjing 210029, Jiangsu, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.affiliation: Nanjing Medical University Nanjing 210029, Jiangsu, China.
authors.forename: Di
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, Jiangsu, China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Model Animal Research Center of Nanjing Medical University Nanjing, Jiangsu 210029, China.
authors.forename: Heling
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Pharmacology, Basic Medical Sciences of Nanjing Medical University Nanjing 210029, Jiangsu, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Li
keywords: PP2A; hypertrophy; knockout mouse model