Dilated cardiomyopathy in transgenic mice expressing a mutant A subunit of protein phosphatase 2A
Autor: | Wolfgang H. Dillmann, Neil Brewis, Kim Ohst, Colin M. Bloor, Howard A. Rockman, Danny M. Chou, Katherine Fields, Antonio Rapacciuolo, Gernot Walter |
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Přispěvatelé: | Brewis, N., Ohst, K., Fields, K., Rapacciuolo, Antonio, Chou, D., Bloor, C., Dillmann, W., Rockman, H., Walter, G. |
Rok vydání: | 2000 |
Předmět: |
Cardiomyopathy
Dilated Genetically modified mouse medicine.medical_specialty Physiology Transgene Protein subunit Mutant Cardiomyopathy Gene Expression Mice Transgenic Biology Mice protein phosphatase 2A core enzyme Physiology (medical) Internal medicine Phosphoprotein Phosphatases medicine Animals Protein Phosphatase 2 Transgenes Muscle Skeletal Genes Dominant Sequence Deletion Myocardium Body Weight heart weight to body weight ratio Skeletal muscle Muscle Smooth Dilated cardiomyopathy Exons Organ Size Protein phosphatase 2 medicine.disease Molecular biology protein phosphatase 2A holoenzyme medicine.anatomical_structure Endocrinology Echocardiography Organ Specificity Mutagenesis Site-Directed Holoenzymes Cardiology and Cardiovascular Medicine Protein Binding |
Zdroj: | Scopus-Elsevier |
ISSN: | 1522-1539 0363-6135 |
Popis: | 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. |
Databáze: | OpenAIRE |
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