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

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dc.contributor.authorCrawley, A.
dc.contributor.authorGliddon, B.
dc.contributor.authorAuclair, D.
dc.contributor.authorBrodie, S.
dc.contributor.authorHirte, C.
dc.contributor.authorKing, B.
dc.contributor.authorFuller, M.
dc.contributor.authorHemsley, K.
dc.contributor.authorHopwood, J.
dc.date.issued2006
dc.description.abstractThe 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-Sgsh(mps3a) 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 110x 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 GM(2)-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-Sgsh(mps3a) MPS IIIA mice. Other behavioral changes include motor, cognitive and sensory deficits, and aggression. Male B6.Cg-Sgsh(mps3a) MPS IIIA mice exhibited more behavioral abnormalities than B6.Cg-Sgsh(mps3a) 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.
dc.description.statementofresponsibilityAllison C. Crawley, Briony L. Gliddon, Dyane Auclair, Suzanne L. Brodie, Craig Hirte, Barbara M. King, Maria Fuller, Kim M. Hemsley, John J. Hopwood
dc.identifier.citationBrain Research, 2006; 1104(1):1-17
dc.identifier.doi10.1016/j.brainres.2006.05.079
dc.identifier.issn0006-8993
dc.identifier.issn1872-6240
dc.identifier.orcidFuller, M. [0000-0001-9092-8942]
dc.identifier.orcidHemsley, K. [0000-0003-1038-9884]
dc.identifier.urihttp://hdl.handle.net/2440/23283
dc.language.isoen
dc.publisherElsevier Science Bv
dc.source.urihttps://doi.org/10.1016/j.brainres.2006.05.079
dc.subjectanimal model
dc.subjectlysosomal storage disease
dc.subjectmucopolysaccharidoses
dc.subjectSanfilippo syndrome
dc.subjectsulfamidase deficiency
dc.subjectmouse behavior
dc.subjectcentral nervous system
dc.subjecttandem mass spectrometry
dc.titleCharacterization of a C57BL/6 congenic mouse strain of mucopolysaccharidosis type IIIA
dc.typeJournal article
pubs.publication-statusPublished

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