Glycosphingolipid storage in Fabry mice extends beyond globotriaosylceramide and is affected by ABCB1 depletion. Future Sci OA 2016 Dec;2(4):FSO147
Date
01/25/2017Pubmed ID
28116130Pubmed Central ID
PMC5242178DOI
10.4155/fsoa-2016-0027Scopus ID
2-s2.0-85043631559 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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.