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

  • Authors:
    • Eun-Sook Park
    • Jin-Ok Choi
    • Joo-Won Park
    • Mi Hee Lee
    • Hae-Young Park
    • Sung-Chul Jung
  • View Affiliations

  • Published online on: September 1, 2009     https://doi.org/10.3892/ijmm_00000246
  • Pages: 401-407
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Abstract

Fabry disease is a lysosomal storage disease caused by a deficiency of α-galactosidase A, which results in aberrant glycosphingolipid metabolism and accumulation of globotriaosylceramide (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 (Saa1), S100 Calcium-binding protein A8 and A9 (S100a8 and a9), and Lipocalin 2 (Lcn2) and renal Neuropeptide 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 Saa1, 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.

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September 2009
Volume 24 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Park E, Choi J, Park J, Lee MH, Park H and Jung S: Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model. Int J Mol Med 24: 401-407, 2009
APA
Park, E., Choi, J., Park, J., Lee, M.H., Park, H., & Jung, S. (2009). Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model. International Journal of Molecular Medicine, 24, 401-407. https://doi.org/10.3892/ijmm_00000246
MLA
Park, E., Choi, J., Park, J., Lee, M. H., Park, H., Jung, S."Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model". International Journal of Molecular Medicine 24.3 (2009): 401-407.
Chicago
Park, E., Choi, J., Park, J., Lee, M. H., Park, H., Jung, S."Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model". International Journal of Molecular Medicine 24, no. 3 (2009): 401-407. https://doi.org/10.3892/ijmm_00000246