A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome)

Mantu Bhaumik, Vivienne J. Muller, Tina Rozaklis, Linda Johnson, Kostantin Dobrenis, Riddhi Bhattacharyya, Sarah Wurzelmann, Peter Finamore, John J. Hopwood, Steven U. Walkley, Pamela Stanley

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Mucopolysaccharidosis type III A (MPS III A, Sanfilippo syndrome) is a rare, autosomal recessive, lysosomal storage disease characterized by accumulation of heparan sulfate secondary to defective function of the lysosomal enzyme heparan N-sulfatase (sulfamidase). Here we describe a spontaneous mouse mutant that replicates many of the features found in MPS III A in children. Brain sections revealed neurons with distended lysosomes filled with membranous and floccular materials with some having a classical zebra body morphology. Storage materials were also present in lysosomes of cells of many other tissues, and these often stained positively with periodic-acid Schiff reagent. Affected mice usually died at 7-10 months of age exhibiting a distended bladder and hepatosplenomegaly. Heparan sulfate isolated from urine and brain had nonreducing end glucosamine-N-sulfate residues that were digested with recombinant human sulfamidase. Enzyme assays of liver and brain extracts revealed a dramatic reduction in sulfamidase activity. Other lysosomal hydrolases that degrade heparan sulfate or other glycans and glycosaminoglycans were either normal, or were somewhat increased in specific activity. The MPS III A mouse provides an excellent model for evaluating pathogenic mechanisms of disease and for testing treatment strategies, including enzyme or cell replacement and gene therapy.

Original languageEnglish (US)
Pages (from-to)1389-1396
Number of pages8
JournalGlycobiology
Volume9
Issue number12
StatePublished - Dec 1999

Fingerprint

Mucopolysaccharidosis III
Heparitin Sulfate
Brain
Enzymes
Gene therapy
Lysosomes
Periodic Acid
Glucosamine
Hydrolases
Glycosaminoglycans
Liver
Sulfates
Neurons
Polysaccharides
Assays
Lysosomal Storage Diseases
Liver Extracts
Tissue
Equidae
Enzyme Assays

Keywords

  • Mouse
  • MPS III A
  • Pathogenesis
  • Sanfilippo syndrome

ASJC Scopus subject areas

  • Biochemistry

Cite this

Bhaumik, M., Muller, V. J., Rozaklis, T., Johnson, L., Dobrenis, K., Bhattacharyya, R., ... Stanley, P. (1999). A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). Glycobiology, 9(12), 1389-1396.

A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). / Bhaumik, Mantu; Muller, Vivienne J.; Rozaklis, Tina; Johnson, Linda; Dobrenis, Kostantin; Bhattacharyya, Riddhi; Wurzelmann, Sarah; Finamore, Peter; Hopwood, John J.; Walkley, Steven U.; Stanley, Pamela.

In: Glycobiology, Vol. 9, No. 12, 12.1999, p. 1389-1396.

Research output: Contribution to journalArticle

Bhaumik, M, Muller, VJ, Rozaklis, T, Johnson, L, Dobrenis, K, Bhattacharyya, R, Wurzelmann, S, Finamore, P, Hopwood, JJ, Walkley, SU & Stanley, P 1999, 'A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome)', Glycobiology, vol. 9, no. 12, pp. 1389-1396.
Bhaumik M, Muller VJ, Rozaklis T, Johnson L, Dobrenis K, Bhattacharyya R et al. A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). Glycobiology. 1999 Dec;9(12):1389-1396.
Bhaumik, Mantu ; Muller, Vivienne J. ; Rozaklis, Tina ; Johnson, Linda ; Dobrenis, Kostantin ; Bhattacharyya, Riddhi ; Wurzelmann, Sarah ; Finamore, Peter ; Hopwood, John J. ; Walkley, Steven U. ; Stanley, Pamela. / A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). In: Glycobiology. 1999 ; Vol. 9, No. 12. pp. 1389-1396.
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