Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (48)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Bhaumik, M.
Right arrow Articles by Stanley, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bhaumik, M.
Right arrow Articles by Stanley, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

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


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
A. Fraldi, K. Hemsley, A. Crawley, A. Lombardi, A. Lau, L. Sutherland, A. Auricchio, A. Ballabio, and J. J. Hopwood
Functional correction of CNS lesions in an MPS-IIIA mouse model by intracerebral AAV-mediated delivery of sulfamidase and SUMF1 genes
Hum. Mol. Genet., November 15, 2007; 16(22): 2693 - 2702.
[Abstract] [Full Text] [PDF]

Home page
 Veterinary PathologyHome page
R. D. Jolly, A. C. Johnstone, E. J. Norman, J. J. Hopwood, and S. U. Walkley
Pathology of Mucopolysaccharidosis IIIA in Huntaway Dogs
Veterinary Pathology, September 1, 2007; 44(5): 569 - 578.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Settembre, I. Annunziata, C. Spampanato, D. Zarcone, G. Cobellis, E. Nusco, E. Zito, C. Tacchetti, M. P. Cosma, and A. Ballabio
Systemic inflammation and neurodegeneration in a mouse model of multiple sulfatase deficiency
PNAS, March 13, 2007; 104(11): 4506 - 4511.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
E. Kelo, U. Dunder, and I. Mononen
Massive accumulation of Man2GlcNAc2-Asn in nonneuronal tissues of glycosylasparaginase-deficient mice and its removal by enzyme replacement therapy
Glycobiology, January 1, 2005; 15(1): 79 - 85.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. Cressant, N. Desmaris, L. Verot, T. Brejot, R. Froissart, M.-T. Vanier, I. Maire, and J. M. Heard
Improved Behavior and Neuropathology in the Mouse Model of Sanfilippo Type IIIB Disease after Adeno-Associated Virus-Mediated Gene Transfer in the Striatum
J. Neurosci., November 10, 2004; 24(45): 10229 - 10239.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Tomatsu, K. O. Orii, C. Vogler, J. Nakayama, B. Levy, J. H. Grubb, M. A. Gutierrez, S. Shim, S. Yamaguchi, T. Nishioka, et al.
Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease
Hum. Mol. Genet., December 15, 2003; 12(24): 3349 - 3358.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Ohmi, D. S. Greenberg, K. S. Rajavel, S. Ryazantsev, H. H. Li, and E. F. Neufeld
Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB
PNAS, February 18, 2003; 100(4): 1902 - 1907.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
R. Bhattacharyya, B. Gliddon, T. Beccari, J. J. Hopwood, and P. Stanley
A novel missense mutation in lysosomal sulfamidase is the basis of MPS III A in a spontaneous mouse mutant
Glycobiology, January 1, 2001; 11(1): 99 - 103.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. H. Li, W.-H. Yu, N. Rozengurt, H.-Z. Zhao, K. M. Lyons, S. Anagnostaras, M. S. Fanselow, K. Suzuki, M. T. Vanier, and E. F. Neufeld
Mouse model of Sanfilippo syndrome type B produced by targeted disruption of the gene encoding alpha -N-acetylglucosaminidase
PNAS, December 7, 1999; 96(25): 14505 - 14510.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.