title: The defects in development and apoptosis of cardiomyocytes in mice lacking the transcriptional factor Pax-8.
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.
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, PR China. Deyeyang203@hotmail.com
authors.forename: Deye
authors.initials: D
authors.lastname: Yang
authors.forename: Dandan
authors.initials: D
authors.lastname: Lai
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Huang
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Shi
authors.forename: Zhan
authors.initials: Z
authors.lastname: Gao
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.forename: Xi
authors.initials: X
authors.lastname: Zhou
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Geng
mesh_terms: 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*
chemical_list: D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I