Characterization of a C57BL/6 congenic mouse strain of mucopolysaccharidosis type IIIA

Allison C. Crawley, Briony L. Gliddon, Dyane Auclair, Suzanne L. Brodie, Craig Hirte, Barbara M. King, Maria Fuller, Kim M. Hemsley, John J. Hopwood

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81 Citations (Scopus)


The original mucopolysaccharidosis type IIIA (MPS IIIA) mice were identified in a mixed background with contributions from four different strains. To ensure long-term stability and genetic homogeneity of this lysosomal storage disease (LSD) model, the aim of this study was to develop and characterize a C57BL/6 congenic strain. The B6.Cg-Sgshmps3a strain compares favorably with the original mixed donor strain, exhibiting low liver sulfamidase activity and significant brain heparan sulfate-derived disaccharide elevation from birth. A rapid increase in brain disaccharide levels occurred after birth, with a plateau reached by 13 weeks of age at 110× the levels observed in brains of age-matched unaffected mice. Typical lysosomal inclusions were observed in cerebral cortical and cerebellar neurons and in liver hepatocytes and Kupffer cells. Ubiquitin-positive spheroids and GM2-ganglioside were also detected in brain. Using the Morris water maze in male mice, impaired memory and spatial learning was evident at 20 weeks of age in B6.Cg-Sgshmps3a MPS IIIA mice. Other behavioral changes include motor, cognitive and sensory deficits, and aggression. Male B6.Cg-Sgshmps3a MPS IIIA mice exhibited more behavioral abnormalities than B6.Cg-Sgshmps3a MPS IIIA females, as observed previously in the original mixed background strain. Affected mice generally survive to 9 to 12 months of age, before death or euthanasia for humane reasons. Overall, minor differences were apparent between the new congenic and previously described mixed MPS IIIA strains. Availability of an in-bred strain will ensure more reproducible experimental outcomes thereby assisting in our goal of developing effective therapies for LSD with central nervous system disease.

Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournalBrain Research
Issue number1
Publication statusPublished - 9 Aug 2006
Externally publishedYes


  • Animal model
  • Central nervous system
  • Lysosomal storage disease
  • Mouse behavior
  • Mucopolysaccharidoses
  • Sanfilippo syndrome
  • Sulfamidase deficiency
  • Tandem mass spectrometry


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