Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach.

Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach. Research Abstract Details 

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Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach. Abstract Text:

David F Moore,Monique P Gelderman,Paulo A Ferreira,Steven R Fuhrmann,Haiqing Yi,Abdel Elkahloun,Lisa M Lix,Roscoe O Brady,Raphael Schiffmann,Ehud Goldin,

Fabry disease is a disorder of alpha-D-galactosyl-containing glycolipids resulting from a deficiency of alpha-galactosidase A. Patients have a poorly understood vascular dysregulation. We hypothesized that disease-related perturbation by using enzyme replacement therapy in the murine model of Fabry disease would provide insight into abnormal biological processes in Fabry disease. Gene expression analyses of the heart, aorta, and liver of male alpha-galactosidase A knockout mice 28 weeks of age were compared with that of WT mice. Microarray analyses were performed before and after six weekly injections of alpha-galactosidase A. Alteration of Rpgrip1 ranked highest statistically in all three organs when knockout mice were compared with WT, and its splice variants responded in a unique way to alpha-galactosidase A. Enzyme replacement therapy tended to not only normalize gene expression, e.g., reduce the overexpression of securin, but also specifically modified gene expression in each tissue examined. Following multiple comparison analysis, gene expression correlation graphs were constructed, and a priori hypotheses were examined by using structural equation modeling. This systems biology approach demonstrated multiple and complex parallel cellular abnormalities in Fabry disease. These abnormalities form the basis for informed, in a Bayesian sense, sequential, hypothesis-driven research that can be subsequently tested experimentally.

Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach. Publishing Authors By Initials

DF Moore,MP Gelderman,PA Ferreira,SR Fuhrmann,H Yi,A Elkahloun,LM Lix,RO Brady,R Schiffmann,E Goldin,

For similar enzymes and coenzymes: enzymes: hydrolases: glycoside hydrolases: galactosidases: alpha-galactosidase research abstracts see: enzymes and coenzymes: enzymes: hydrolases: glycoside hydrolases: galactosidases: alpha-galactosidase research

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Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Intr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 8065-70

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 30

MONTH: 04

YEAR: 2007

Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach. Keywords Mesh Terms:

KEYWORDS: alpha-Galactosidase

MESH TERMS: therapeutic use

Chemical & Substance for Abstract: Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach. Information

Substance Name: alpha-Galactosidase

Registry Number: EC 3.2.1.22

Grant and Affiliation Information for Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach.

AFFILIATION: Section of Neurology, University of Manitoba, Winnipeg, MB, Canada R3T 2N2.

Country: United States

AGENCY: United States NEI

GRANT: EY 11993

ACRONYM: EY

MEDLINETA: Proc Natl Acad Sci U S A

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