The defects in development and apoptosis of cardiomyocytes in mice lacking the transcriptional factor Pax-8.
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.
Yang
Deye
D
The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, PR China. Deyeyang203@hotmail.com
Lai
Dandan
D
Huang
Xiaoyan
X
Shi
Xiangxiang
X
Gao
Zhan
Z
Huang
Fang
F
Zhou
Xi
X
Geng
Yong-Jian
YJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000172:deficiency / Q000235:genetics; D002478:Cells, Cultured; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000172:deficiency / Q000235:genetics*
D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I