title: A novel missense mutation in lysosomal sulfamidase is the basis of MPS III A in a spontaneous mouse mutant.
abstract: Sanfilippo syndrome type III A (Mucopolysaccharidosis (MPS) III A) is a rare, autosomal recessive, lysosomal storage disease, characterized by the accumulation of heparan sulfate and the loss of function of lysosomal heparan N-sulfatase activity. The disease leads to devastating mental and physical consequences and a mouse model that can be used to explore gene therapy and enzyme or cell replacement therapies is needed. We have previously identified a mouse with low sulfamidase activity and symptoms and pathologies typical of MPS III A (Bhaumik, M., Muller, V. J., Rozaklis, T., Johnson, L., Dobrenis, K., Bhattacharyya, R., Wurzelmann, S., Finamore, P., Hopwood, J. J., Walkley, S. U., and Stanley, P. [1999] A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). Glycobiology 9, 1389--1396). We now show that the sulfamidase gene of the MPS III A mouse carries a novel mutation (G91A) that gives an amino acid change (D31N) likely to interfere with the coordination of a divalent metal ion in the active site of this sulfatase. This spontaneous mouse mutant is an excellent model for MPS III A in humans as this disease often arises due to a missense mutation in lysosomal sulfamidase.
authors.affiliation: Department of Cell Biology, Albert Einstein College Medicine, New York, NY 10461, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bhattacharyya
authors.forename: B
authors.initials: B
authors.lastname: Gliddon
authors.forename: T
authors.initials: T
authors.lastname: Beccari
authors.forename: J J
authors.initials: JJ
authors.lastname: Hopwood
authors.forename: P
authors.initials: P
authors.lastname: Stanley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D017931:DNA Primers; D018076:DNA, Complementary; D004195:Disease Models, Animal; D006867:Hydrolases / Q000235:genetics*; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009084:Mucopolysaccharidosis III / Q000201:enzymology / Q000235:genetics*; D020125:Mutation, Missense; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase