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.