Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model

Eun Sook Park, Jin Ok Choi, Joo Won Park, Mi Hee Lee, Hae Young Park, Sung Chul Jung

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Fabry disease is a lysosomal storage disease caused by a deficiency of α-galactosidase A, which results in aberrant glycosphingolipid metabolism and accumulation of globo-triaosylceramide (Gb3). Since a correlation between the level of Gb3 and clinical manifestations of Fabry disease has not been observed, we investigated potential diagnostic biomarkers. Hepatic and renal gene expression of male α-galactosidase A-deficient mice (Fabry mice) was compared with that of wild-type mice. Microarray analyses were performed using samples taken before and after intravenous infusion of α-galactosidase A. The identified genes were validated using quantitative real-time PCR and Western blot assay. Expression of hepatic Serum Amyloid A1 (Saal), S 100 Calcium-binding protein A8 and A9 (S100a8 and a9), and Lipocalin 2 (Lcn2) and renal Neuro-peptide Y (Npy), Thrombospondin 2 and 4 (Tsp-2 and -4) was significantly upregulated in Fabry mice compared with wild-type mice and normalized by enzyme replacement therapy. Plasma concentrations of Lcn2 and Npy were also greater in Fabry mice and reduced to wild-type levels after enzyme replacement therapy, although the plasma concentrations of these proteins show heterogeneity. Upregulation of Saal, S100a8, S100a9 and Lcn2 may modulate inflammation and Lcn2, Npy and Tsp may be associated with vascular and renal involvement in Fabry disease. Furthermore, these genes are promising targets for developing biomarkers for monitoring disease progression and therapeutic efficacy in patients with Fabry disease.

Original languageEnglish
Pages (from-to)401-407
Number of pages7
JournalInternational Journal of Molecular Medicine
Issue number3
StatePublished - 2009


  • Biomarker
  • Fabry disease
  • Gene expression
  • Lipocalin2
  • Microarray
  • Mouse
  • Neuropeptide Y
  • α-galactosidase A


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