Altered brain gene expression profiles associated with the pathogenesis of phenylketonuria in a mouse model

Joo Won Park, Eun Sook Park, Eun Nam Choi, Hae Young Park, Sung Chul Jung

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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 Pahenu2 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), α-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.

Original languageEnglish
Pages (from-to)90-99
Number of pages10
JournalClinica Chimica Acta
Issue number1-2
StatePublished - Mar 2009

Bibliographical note

Funding Information:
This study was supported by a Korean Health 21 R&D Project from the Ministry of Health and Welfare, Republic of Korea (A010384).


  • Biomarker
  • Brain
  • Klotho
  • Mouse
  • Phenylketonuria
  • Transthyretin


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