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 journalArticlepeer-review

155 Scopus citations


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
Issue number12
StatePublished - Dec 1999


  • Mouse
  • Pathogenesis
  • Sanfilippo syndrome

ASJC Scopus subject areas

  • General Medicine


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