TY - JOUR
T1 - A novel missense mutation in lysosomal sulfamidase is the basis of MPS III A in a spontaneous mouse mutant
AU - Bhattacharyya, Riddhi
AU - Gliddon, Briony
AU - Beccari, Tommaso
AU - Hopwood, John J.
AU - Stanley, Pamela
N1 - Funding Information:
This research was partly funded by the Coordenação de Aperfeiçoamento de ? essoal de Nível Superior – Brasil 縀CAPES 缀 W Financial Code ?
Funding Information:
This research was partly funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Financial Code 001.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - MPS III A
KW - Point mutation
KW - Sanfilippo syndrome
KW - Sulfamidase
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U2 - 10.1093/glycob/11.1.99
DO - 10.1093/glycob/11.1.99
M3 - Article
C2 - 11181566
AN - SCOPUS:0035092770
SN - 0959-6658
VL - 11
SP - 99
EP - 103
JO - Glycobiology
JF - Glycobiology
IS - 1
ER -