title: [Abnormal development of conotruncal region in Cx43 knockout mice].
abstract: OBJECTIVE
  To explore the etiology of the conotruncal malformations in Cx43 knockout mice.
  
  
  METHODS
  The objects were C57/BL6 mice of E11.5 to 1 day after birth by the mating of 2 month old heterozygous mice which included Cx43 (knockout, KO) homozygotes (Cx43-/-), heterozygotes (Cx43+/-) and wild-types (Cx43+/+) genotyped by PCR method. Microdissection and HE staining were used to examine the structures of hearts. The expression of the alpha-SCA, alpha-SMA, AP-2alpha were detected by immunohistochemistry. AP-2alpha mRNA was detected by in situ hybridization.
  
  
  RESULTS
  Cx43-/- mice died within 24 h after birth with a swelling and blockage of the conotruncal region, which led to the obstruction of OFT and enlargement of right ventricle. HE staining showed plenty of abnormal tissues in this region forming many pouches. No apparent malformations were observed in Cx43+/- and Cx43+/+ mice. The expression of alpha-SCA in the proximal OFT septum was delayed obviously in Cx43-/- predominantly at E13.5 and E14.5. The expression of alpha-SMA in the OFT in Cx43+/- and Cx43-/- was stronger than that of Cx43+/+ mice, and mostly located in the hyperplastic conotruncal region especially at E13.5-E15.5 in Cx43-/- mice. The expression could still be observed at the birth day in Cx43-/- mice, which was not observed in Cx43+/+ mice. The expression of AP-2alpha and AP-2alpha mRNA at E13.5 increased in Cx43-/- and abnormally located in the proximal OFT septum.
  
  
  CONCLUSIONS
  Cx43 KO mice are characterized by hyperplasia in conotruncal region. Cx43 KO mice exhibited a delayed myocardialization and the developmental immaturity of cardiomyocytes. The abnormal distribution of cardiac neural crest cells is likely to contribute to the conotruncal malformations in Cx43-deficient mice.
authors.affiliation: Pediatric Heart Center, Children's Hospital of Fudan University, Shanghai 200032, China.
authors.forename: Xiao-qing
authors.initials: XQ
authors.lastname: Zhao
authors.forename: Guo-ying
authors.initials: GY
authors.lastname: Huang
authors.forename: Li-jian
authors.initials: LJ
authors.lastname: Xie
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.forename: Guo-min
authors.initials: GM
authors.lastname: Zhou
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000235:genetics*; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D018031:Connexin 43