Faculty Collaboration Database

Glycosphingolipid storage in Fabry mice extends beyond globotriaosylceramide and is affected by ABCB1 depletion. Future Sci OA 2016 Dec;2(4):FSO147

Date

01/25/2017

Pubmed ID

28116130

Pubmed Central ID

PMC5242178

DOI

10.4155/fsoa-2016-0027

Scopus ID

2-s2.0-85043631559 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

AIM: Fabry disease is caused by α-galactosidase A deficiency leading to accumulation of globotriaosylceramide (Gb₃) in tissues. Clinical manifestations do not appear to correlate with total Gb₃ levels. Studies examining tissue distribution of specific acyl chain species of Gb₃ and upstream glycosphingolipids are lacking.

MATERIAL & METHODS/RESULTS: Thorough characterization of the Fabry mouse sphingolipid profile by LC-MS revealed unique Gb₃ acyl chain storage profiles. Storage extended beyond Gb₃; all Fabry tissues also accumulated monohexosylceramides. Depletion of ABCB1 had a complex effect on glycosphingolipid storage.

CONCLUSION: These data provide insights into how specific sphingolipid species correlate with one another and how these correlations change in the α-galactosidase A-deficient state, potentially leading to the identification of more specific biomarkers of Fabry disease.

Author List

Kamani MA, Provençal P, Boutin M, Pacienza N, Fan X, Novak A, Huang TC, Binnington B, Au BC, Auray-Blais C, Lingwood CA, Medin JA

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin