I型粘多糖病
Hurler综合征
近交系
拉伤
化学
作者
Allison C. Crawley,Briony L. Gliddon,Dyane Auclair,Suzanne L. Brodie,Craig Hirte,Barbara King,Maria Fuller,Kim M. Hemsley,John J. Hopwood
出处
期刊:Brain Research
[Elsevier]
日期:2006-08-09
卷期号:1104 (1): 1-17
被引量:81
标识
DOI:10.1016/j.brainres.2006.05.079
摘要
Abstract 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-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 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 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.
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