PMID- 10561464
OWN - NLM
STAT- MEDLINE
DCOM- 20000201
LR  - 20190513
IS  - 0959-6658 (Print)
IS  - 0959-6658 (Linking)
VI  - 9
IP  - 12
DP  - 1999 Dec
TI  - A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome).
PG  - 1389-96
AB  - Mucopolysaccharidosis type III A (MPS III A, Sanfilippo syndrome) is a rare,
      autosomal recessive, lysosomal storage disease characterized by accumulation of
      heparan sulfate secondary to defective function of the lysosomal enzyme heparan
      N- sulfatase (sulfamidase). Here we describe a spontaneous mouse mutant that
      replicates many of the features found in MPS III A in children. Brain sections
      revealed neurons with distended lysosomes filled with membranous and floccular
      materials with some having a classical zebra body morphology. Storage materials
      were also present in lysosomes of cells of many other tissues, and these often
      stained positively with periodic-acid Schiff reagent. Affected mice usually died 
      at 7-10 months of age exhibiting a distended bladder and hepatosplenomegaly.
      Heparan sulfate isolated from urine and brain had nonreducing end glucosamine- N 
      -sulfate residues that were digested with recombinant human sulfamidase. Enzyme
      assays of liver and brain extracts revealed a dramatic reduction in sulfamidase
      activity. Other lysosomal hydrolases that degrade heparan sulfate or other
      glycans and glycosaminoglycans were either normal, or were somewhat increased in 
      specific activity. The MPS III A mouse provides an excellent model for evaluating
      pathogenic mechanisms of disease and for testing treatment strategies, including 
      enzyme or cell replacement and gene therapy.
FAU - Bhaumik, M
AU  - Bhaumik M
AD  - Department of Cell Biology, Albert Einstein College of Medicine, New York, NY
      10461, USA.
FAU - Muller, V J
AU  - Muller VJ
FAU - Rozaklis, T
AU  - Rozaklis T
FAU - Johnson, L
AU  - Johnson L
FAU - Dobrenis, K
AU  - Dobrenis K
FAU - Bhattacharyya, R
AU  - Bhattacharyya R
FAU - Wurzelmann, S
AU  - Wurzelmann S
FAU - Finamore, P
AU  - Finamore P
FAU - Hopwood, J J
AU  - Hopwood JJ
FAU - Walkley, S U
AU  - Walkley SU
FAU - Stanley, P
AU  - Stanley P
LA  - eng
GR  - R01 32169/PHS HHS/United States
GR  - R37 30645/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Glycobiology
JT  - Glycobiology
JID - 9104124
RN  - 0 (Glycosaminoglycans)
RN  - 9050-30-0 (Heparitin Sulfate)
RN  - EC 3.- (Hydrolases)
SB  - IM
MH  - Animals
MH  - Brain/ultrastructure
MH  - *Disease Models, Animal
MH  - Female
MH  - Glycosaminoglycans/analysis/urine
MH  - Heparitin Sulfate/urine
MH  - Humans
MH  - Hydrolases/metabolism
MH  - Liver/ultrastructure
MH  - Lysosomes/enzymology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Microscopy, Electron
MH  - *Mucopolysaccharidosis III/metabolism/pathology
MH  - Myocardium/pathology
MH  - Spleen/ultrastructure
MH  - Urinary Bladder/pathology
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - cwc133 [pii]
AID - 10.1093/glycob/9.12.1389 [doi]
PST - ppublish
SO  - Glycobiology. 1999 Dec;9(12):1389-96. doi: 10.1093/glycob/9.12.1389.