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Int J Cardiol. 2012 Jan 12;154(1):43-51. doi: 10.1016/j.ijcard.2010.08.057. Epub 2010 Sep 20.

The defects in development and apoptosis of cardiomyocytes in mice lacking the transcriptional factor Pax-8.

Author information

1
The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, PR China. Deyeyang203@hotmail.com

Abstract

BACKGROUND:

Cardiac-specific deletion of ALK3 is lethal in mid-gestation with ventricular septum malformations (VSM). This study was designed to define the Pax-8's role in heart development and cardiomyocyte apoptosis.

METHODS:

Pathologic changes in the hearts of Pax-8 or ALK3 knockout and wild type control mice were determined by light and electron microscopy. Analysis of cardiomyocyte apoptosis was performed by TUNEL. The effect of Pax-8 gene deficiency on caspase-3 activity was examined after transfecting Pax-8 siRNA into cultured myoblast cell line.

RESULTS:

Mice with ALK3 or Pax-8 gene knockout but not wild type control animals showed the development of VSM. Increased cardiomyocyte apoptosis was found in homozygotes. Echocardiography showed that Pax-8 homozygote mice developed malfunction of the heart. Furthermore, the caspase-3 activity was significantly higher in the cells treated with Pax-8 siRNA as compared to those treated with negative control siRNA in H9C2 (2-1) cell line.

CONCLUSIONS:

The Pax-8 gene may play a crucial role in heart development and regulating cardiocyte apoptosis. Knockout of Pax-8 may exert a similar effect on myocardial morphology and apoptosis as those seen in ALK3 knockouts. Furthermore, the ventricular septum malformations could be partially attributed to accelerated cardiomyocyte apoptosis.

PMID:
20851479
DOI:
10.1016/j.ijcard.2010.08.057
[Indexed for MEDLINE]

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