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Glycobiology, 1999, Vol. 9, No. 12 1389-1396
© 1999 Oxford University Press

A mouse model for mucopolysaccharidosistype III A (Sanfilippo syndrome)

Mantu Bhaumik, Vivienne J.Muller3, Tina Rozaklis3, Linda Johnson2, Kostantin Dobrenis3, Riddhi Bhattacharyya, Sarah Wurzelmann3, Peter Finamore3, John J.Hopwood4, Steven U.Walkleya,3 and Pamela Stanleya

Departments of Cell Biology, 2Pathology,and 3Neuroscience, AlbertEinstein College Medicine, New York, NY 10461, USA and 4Lysosomal Diseases Research Unit,The Women’s and Children’s Hospital, Adelaide,South Australia, 5006, Australia

Mucopolysaccharidosis type III A (MPS III A, Sanfilippo syndrome)is a rare, autosomal recessive, lysosomal storage disease characterizedby accumulation of heparan sulfate secondary to defective functionof the lysosomal enzyme heparan N-sulfatase (sulfamidase).Here we describe a spontaneous mouse mutant that replicates manyof the features found in MPS III A in children. Brain sections revealedneurons with distended lysosomes filled with membranous and floccularmaterials with some having a classical zebra body morphology. Storagematerials were also present in lysosomes of cells of many othertissues, and these often stained positively with periodic-acid Schiffreagent. Affected mice usually died at 7–10 months of age exhibitinga distended bladder and hepatosplenomegaly. Heparan sulfate isolatedfrom urine and brain had nonreducing end glucosamine-N-sulfateresidues that were digested with recombinant human sulfamidase.Enzyme assays of liver and brain extracts revealed a dramatic reductionin sulfamidase activity. Other lysosomal hydrolases that degradeheparan sulfate or other glycans and glycosaminoglycans were eithernormal, or were somewhat increased in specific activity. The MPSIII A mouse provides an excellent model for evaluating pathogenicmechanisms of disease and for testing treatment strategies, includingenzyme or cell replacement and gene therapy.

a To whom correspondence should be addressed at:Department of Cell Biology, Albert Einstein College Medicine, 1300Morris Park, New York, NY 10461


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