| First Author | Bhaumik M | Year | 1999 |
| Journal | Glycobiology | Volume | 9 |
| Issue | 12 | Pages | 1389-96 |
| PubMed ID | 10561464 | Mgi Jnum | J:72142 |
| Mgi Id | MGI:2151820 | Doi | 10.1093/glycob/9.12.1389 |
| Citation | Bhaumik M, et al. (1999) A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). Glycobiology 9(12):1389-96 |
| abstractText | 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. |
