Stabilised beta-catenin in postnatal ventricular myocardium leads to dilated cardiomyopathy and premature death.
Beta-catenin is a component of the intercalated disc in cardiomyocytes, but can also be involved in signalling and activation of gene transcription. We wanted to determine how long-term changes in beta-catenin expression levels would affect mature cardiomyocytes. Conditional transgenic mice that either lacked beta-catenin or that expressed a non-degradable form of beta-catenin in the adult ventricle were created. While mice lacking beta-catenin in the ventricle do not have an overt phenotype, mice expressing a non-degradable form develop dilated cardiomyopathy and do not survive beyond 5 months. A detailed analysis could reveal that this phenotype is correlated with a distinct localisation of beta-catenin in adult cardiomyocytes, which cannot be detected in the nucleus, no matter how much protein is present. Our report is the first study that addresses long-term effects of either the absence of beta-catenin or its stabilisation on ventricular cardiomyocytes and it suggests that beta-catenin's role in the nucleus may be of little significance in the healthy adult heart.
Hirschy
Alain
A
Institute of Cell Biology, ETH Zurich-Hönggerberg, Switzerland.
Croquelois
Adrien
A
Perriard
Evelyne
E
Schoenauer
Roman
R
Agarkova
Irina
I
Hoerstrup
Simon P
SP
Taketo
Makoto M
MM
Pedrazzini
Thierry
T
Perriard
Jean-Claude
JC
Ehler
Elisabeth
E
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology*; D002458:Cell Fractionation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D055879:Gene Knock-In Techniques / Q000379:methods; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019426:Integrases / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D015996:Survival Rate; D014158:Transcription, Genetic / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism*
C495267:CTNNB1 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin; C045073:Cre recombinase; D019426:Integrases