title: Distribution of Heparan Sulfate Oligosaccharides in Murine Mucopolysaccharidosis Type IIIA.
abstract: Heparan sulfate (HS) catabolism begins with endo-degradation of the polysaccharide to smaller HS oligosaccharides, followed by the sequential action of exo-enzymes to reduce these oligosaccharides to monosaccharides and inorganic sulfate. In mucopolysaccharidosis type IIIA (MPS IIIA) the exo-enzyme, N-sulfoglucosamine sulfohydrolase, is deficient resulting in an inability to hydrolyze non-reducing end glucosamine N-sulfate esters. Consequently, partially degraded HS oligosaccharides with non-reducing end glucosamine sulfate esters accumulate. We investigated the distribution of these HS oligosaccharides in tissues of a mouse model of MPS IIIA using high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Oligosaccharide levels were compared to total uronic acid (UA), which was used as a measure of total glycosaminoglycan. Ten oligosaccharides, ranging in size from di- to hexasaccharides, were present in all the tissues examined including brain, spleen, lung, heart, liver, kidney and urine. However, the relative levels varied up to 10-fold, suggesting different levels of HS turnover and storage. The relationship between the di- and tetrasaccharides and total UA was tissue specific with spleen and kidney showing a different disaccharide:total UA ratio than the other tissues. The hexasaccharides showed a stronger correlation with total UA in all tissue types suggesting that hexasaccharides may more accurately reflect the storage burden in these tissues.
authors.affiliation: Forensic Science South Australia, 21 Divett Place, Adelaide, South Australia 5000, Australia. kerryn.mason@sa.gov.au.
authors.forename: Kerryn
authors.initials: K
authors.lastname: Mason
authors.affiliation: Baker ID Heart and Diabetes Institute, 75 Commercial Road, Melbourne, Victoria 3006, Australia. peter.meikle@bakeridi.edu.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Meikle
authors.affiliation: SAHMRI, North Terrace, Adelaide, South Australia, 5000 Australia. john.hopwood@sahmri.com.
authors.forename: John
authors.initials: J
authors.lastname: Hopwood
authors.affiliation: SA Pathology at Women's and Children's Hospital, 72 King William Road, North Adelaide 5006, Australia. maria.fuller@adelaide.edu.au.
authors.forename: Maria
authors.initials: M
authors.lastname: Fuller