Dilated cardiomyopathy in transgenic mice expressing a mutant A subunit of protein phosphatase 2A.

Journal Article (Journal Article)

The protein phosphatase 2A (PP2A) holoenzyme consists of a catalytic subunit, C, and two regulatory subunits, A and B. The PP2A core enzyme is composed of subunits A and C. Both the holoenzyme and the core enzyme are similarly abundant in heart tissue. Transgenic mice were generated expressing high levels of a dominant negative mutant of the A subunit (A delta 5) in the heart, skeletal muscle, and smooth muscle that competes with the endogenous A subunit for binding the C subunit but does not bind B subunits. We found that the ratio of core enzyme to holoenzyme was increased in A delta 5-expressing hearts. Importantly, already at day 1 after birth, A delta 5-transgenic mice had an increased heart weight-to-body weight ratio that persisted throughout life. Echocardiographic analysis of A delta 5-transgenic hearts revealed increased end-diastolic and end-systolic dimensions and decreased fractional shortening. In addition, the thickness of the septum and of the left ventricular posterior wall was significantly reduced. On the basis of these findings, we consider the heart phenotype of A delta 5-transgenic mice to be a form of dilated cardiomyopathy that frequently leads to premature death.

Full Text

Duke Authors

Cited Authors

  • Brewis, N; Ohst, K; Fields, K; Rapacciuolo, A; Chou, D; Bloor, C; Dillmann, W; Rockman, H; Walter, G

Published Date

  • September 2000

Published In

Volume / Issue

  • 279 / 3

Start / End Page

  • H1307 - H1318

PubMed ID

  • 10993798

International Standard Serial Number (ISSN)

  • 0363-6135

Digital Object Identifier (DOI)

  • 10.1152/ajpheart.2000.279.3.H1307

Language

  • eng

Conference Location

  • United States