2. Academic Validation
  3. Relative distribution of Gb3 isoforms/analogs in NOD/SCID/Fabry mice tissues determined by tandem mass spectrometry

Relative distribution of Gb3 isoforms/analogs in NOD/SCID/Fabry mice tissues determined by tandem mass spectrometry

  • Bioanalysis. 2016 Sep;8(17):1793-807. doi: 10.4155/bio-2016-0116.
Philippe Provençal 1,  Michel Boutin 1,  Shaalee Dworski 2,  Bryan Au 2,  Jeffrey A Medin 2 3,  Christiane Auray-Blais 1
Affiliations

Affiliations

  • 1 Department of Pediatrics, Division of Medical Genetics, Faculty of Medicine & Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, J1H 5N4 Canada.
  • 2 Institute of Medical Science, Max Bell Research Center, University of Toronto, 101 College Street, Room 5-407, Toronto, ON, M5G 1L7 Canada.
  • 3 Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, MFRC 3018, Milwaukee, WI 53226, USA.
PMID: 27523577 DOI: 10.4155/bio-2016-0116
Abstract

Aim: Fabry disease is a lysosomal storage disorder leading to glycosphingolipid accumulation in different organs, tissues and biological fluids. The development of a Fabry disease gene therapy trial is underway in Canada. A tool to determine the distribution of Gb3 biomarkers in tissues of Fabry mice might be applicable to monitor the effect of gene therapy. Results & methodology: An ultra-performance LC-MS/MS (UPLC-MS/MS) method for the analysis of 22 Gb3 isoform/analogs in various Fabry mice tissues was developed and validated. Marked variation in biomarker organ distribution was found with higher levels in the spleen, followed by the small intestine, kidneys, lungs, heart, liver and brain.

Conclusion: The devised method is sensitive and useful for the evaluation of biomarker profiles in Fabry mice.

Keywords

Fabry disease; MS; NOD/SCID mice; globotriaosylceramide; isoforms/analogs; liquid–liquid extraction; organ biomarker distribution.

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