title: Transcription profiles of the ductus arteriosus in Brown-Norway rats with irregular elastic fiber formation.
abstract: BACKGROUND
  Patent ductus arteriosus (PDA) is one of the most common congenital cardiovascular defects in children. The Brown-Norway (BN) inbred rat presents a higher frequency of PDA. A previous study reported that 2 different quantitative trait loci on chromosomes 8 and 9 were significantly linked to PDA in this strain. Nevertheless, the genetic or molecular mechanisms underlying PDA phenotypes in BN rats have not been fully investigated yet.
  
  
  RESULTS
  It was found that the elastic fibers were abundant in the subendothelial area but scarce in the media even in the closed ductus arteriosus (DA) of full-term BN neonates. DNA microarray analysis identified 52 upregulated genes (fold difference >2.5) and 23 downregulated genes (fold difference <0.4) when compared with those of F344 control neonates. Among these genes, 8 (Tbx20, Scn3b, Stac, Sphkap, Trpm8, Rup2, Slc37a2, and RGD1561216) are located in chromosomes 8 and 9. Interestingly, it was also suggested that the significant decrease in the expression levels of the PGE2-specfic receptor, EP4, plays a critical role in elastogenesis in the DA.
  
  
  CONCLUSIONS
  BN rats exhibited dysregulation of elastogenesis in the DA. DNA microarray analysis identified the candidate genes including EP4 involved in the DNA phenotype. Further investigation of these newly identified genes will hopefully clarify the molecular mechanisms underlying the irregular formation of elastic fibers in PDA.
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Hsieh
authors.forename: Norika Mengchia
authors.initials: NM
authors.lastname: Liu
authors.forename: Eriko
authors.initials: E
authors.lastname: Ohmori
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yokota
authors.forename: Ichige
authors.initials: I
authors.lastname: Kajimura
authors.forename: Toru
authors.initials: T
authors.lastname: Akaike
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Goda
authors.forename: Susumu
authors.initials: S
authors.lastname: Minamisawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D033481:Chromosomes, Mammalian / Q000235:genetics; D004373:Ductus Arteriosus / Q000378:metabolism* / Q000473:pathology; D004374:Ductus Arteriosus, Patent / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004547:Elastic Tissue / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D040641:Quantitative Trait Loci; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic
chemical_list: D009124:Muscle Proteins