title: Altered brain gene expression profiles associated with the pathogenesis of phenylketonuria in a mouse model.
abstract: BACKGROUND
  Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine. The resultant hyperphenylalaninemia causes mental retardation, seizure, and abnormalities in behavior and movement.
  
  
  METHODS
  We analyzed gene expression profiles in brain tissues of Pah(enu2) mice to elucidate the mechanisms involved in phenylalanine-induced neurological damage. The altered gene expression was confirmed by real-time PCR and Western blotting. To identify markers associated with neurological damage, we examined TTR expression in serum by Western blotting.
  
  
  RESULTS
  Gene expression profiling of brain tissue from a mouse model of PKU revealed overexpression of transthyretin (Ttr), sclerostin domain containing 1 (Sostdc1), alpha-Klotho (Kl), prolactin receptor (Prlr), and early growth response 2 (Egr2). In contrast to its overexpression in the brain, TTR expression was low in the sera of PKU mice offered unrestricted access to a diet containing phenylalanine. Expression of TTR decreased in a time-dependent manner in phenylalanine-treated HepG2 cells.
  
  
  CONCLUSIONS
  These findings indicate that Ttr, Sostdc1, Kl, Prlr, and Egr2 can be involved in the pathogenesis of PKU and that phenylalanine might have a direct effect on the level of TTR in serum.
authors.affiliation: Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, South Korea.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Park
authors.forename: Eun Nam
authors.initials: EN
authors.lastname: Choi
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Jung
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D051767:Early Growth Response Protein 2 / Q000235:genetics; D020869:Gene Expression Profiling; D005966:Glucuronidase / Q000235:genetics; D000090265:Klotho Proteins; D051379:Mice; D010661:Phenylketonurias / Q000235:genetics*; D011228:Prealbumin / Q000235:genetics; D011981:Receptors, Prolactin / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D011228:Prealbumin; D011981:Receptors, Prolactin; C483887:Sostdc1 protein, mouse; D005966:Glucuronidase; D000090265:Klotho Proteins