A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome)
Date
1999
Authors
Bhaumik, M.
Muller, V.
Rozaklis, T.
Johnson, L.
Dobrenis, K.
Bhattacharyya, R.
Wurzelmann, S.
Finamore, P.
Hopwood, J.
Walkley, S.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Glycobiology, 1999; 9(12):1389-1396
Statement of Responsibility
Mantu Bhaumik, Vivienne J.Muller, Tina Rozaklis, Linda Johnson, Kostantin Dobrenis, Riddhi Bhattacharyya, Sarah Wurzelmann, Peter Finamore, John J.Hopwood, Steven U.Walkleya, and Pamela Stanley
Conference Name
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.
School/Discipline
Dissertation Note
Provenance
Description
Copyright © 1999 Oxford University Press