title: Glycosphingolipid storage in Fabry mice extends beyond globotriaosylceramide and is affected by ABCB1 depletion.
abstract: OBJECTIVE
  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 Gb3levels. Studies examining tissue distribution of specific acyl chain species of Gb3and upstream glycosphingolipids are lacking.
  Thorough characterization of the Fabry mouse sphingolipid profile by LC-MS revealed unique Gb3acyl chain storage profiles. Storage extended beyond Gb3; all Fabry tissues also accumulated monohexosylceramides. Depletion of ABCB1 had a complex effect on glycosphingolipid storage.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Health Network, Toronto, Ontario, M5G 1L7, Canada; University Health Network, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Mustafa A
authors.initials: MA
authors.lastname: Kamani
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Université de Sherbrooke, CHUS, Hospital Fleurimont, Sherbrooke, Quebec, J1H 5N4, Canada; Department of Pediatrics, Division of Medical Genetics, Université de Sherbrooke, CHUS, Hospital Fleurimont, Sherbrooke, Quebec, J1H 5N4, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Provençal
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Université de Sherbrooke, CHUS, Hospital Fleurimont, Sherbrooke, Quebec, J1H 5N4, Canada; Department of Pediatrics, Division of Medical Genetics, Université de Sherbrooke, CHUS, Hospital Fleurimont, Sherbrooke, Quebec, J1H 5N4, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Boutin
authors.affiliation: University Health Network, Toronto, Ontario, M5G 1L7, Canada; University Health Network, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pacienza
authors.affiliation: University Health Network, Toronto, Ontario, M5G 1L7, Canada; University Health Network, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
authors.affiliation: Division of Molecular Structure & Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada; Division of Molecular Structure & Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
authors.forename: Anton
authors.initials: A
authors.lastname: Novak
authors.affiliation: University Health Network, Toronto, Ontario, M5G 1L7, Canada; University Health Network, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Tonny C
authors.initials: TC
authors.lastname: Huang
authors.affiliation: Division of Molecular Structure & Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada; Division of Molecular Structure & Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
authors.forename: Beth
authors.initials: B
authors.lastname: Binnington
authors.affiliation: University Health Network, Toronto, Ontario, M5G 1L7, Canada; University Health Network, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Au
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Université de Sherbrooke, CHUS, Hospital Fleurimont, Sherbrooke, Quebec, J1H 5N4, Canada; Department of Pediatrics, Division of Medical Genetics, Université de Sherbrooke, CHUS, Hospital Fleurimont, Sherbrooke, Quebec, J1H 5N4, Canada.
authors.forename: Christiane
authors.initials: C
authors.lastname: Auray-Blais
authors.affiliation: Division of Molecular Structure & Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada; Departments of Biochemistry & Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada; Division of Molecular Structure & Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada; Departments of Biochemistry & Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lingwood
authors.affiliation: University Health Network, Toronto, Ontario, M5G 1L7, Canada; Department of Medical Biophysics, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, M5S 1A8, Canada; University Health Network, Toronto, Ontario, M5G 1L7, Canada; Department of Medical Biophysics, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Medin
keywords: ceramides; lipidomics; lysosomal storage disorders