A novel missense mutation in lysosomal sulfamidase is the basis of MPS III A in a spontaneous mouse mutant

Riddhi Bhattacharyya, Briony Gliddon, Tommaso Beccari, John J. Hopwood, Pamela Stanley

Research output: Contribution to journalArticle

61 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)99-103
Number of pages5
JournalGlycobiology
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2001

Keywords

  • MPS III A
  • Point mutation
  • Sanfilippo syndrome
  • Sulfamidase

ASJC Scopus subject areas

  • Biochemistry

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