Journal of mucopolysaccharidosis and rare diseases

Association for Research of MPS and Rare Diseases (뮤코다당증연구학회)
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Phenotypic Characterization of MPS IIIA (Sgshmps3a/ Sgshmps3a) Mouse Model

  • Park, Sung Won (Department of Pediatircs, Cheil General Hospital and Womens' Health Care Center, Dankook University College of Medicine) ;
  • Ko, Ara (Research Institute for Future Medicine, Samsung Medical Center) ;
  • Jin, Dong-kyu (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2018.06.15
  • Accepted : 2018.06.19
  • Published : 2018.06.30
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Abstract

Mucopolysaccharidosis IIIA is a heritable neurodegenerative disorder resulting from the dysfunction of the lysosomal hydrolase sulphamidase. This leads to the primary accumulation of the complex carbohydrate heparan sulphate in a wide range of tissues and CNS degeneration. Characterization of animal model is the beginning point of the therapeutic clinical trial. Mouse model has a limitation in that it is not a human and does not have all of the disease phenotypes. Therefore, delineate of the phenotypic characteristics of MPS IIIA mouse model prerequisite for the enzyme replace treatment for the diseases. We designed 6-month duration of phenotypic characterization of MPS IIIA mouse biochemically, behaviorally and histologically. We compared height and weight of MPS IIIA mouse with wild type from 4 weeks to 6 months in both male and female. At 6 months, we measured GAG storage in urine kidney, heart, liver, lung and spleen. The brain GAG storage is presented with Alcian blue staining, immunohistochemistry, and electron-microscopy. The neurologic phenotype is evaluated by brain MRI and behavioral study including open field test, fear conditioning, T-maze test and Y-maze test. Especially behavioral tests were done serially at 4month and 6month. This study will show the result of the MPS IIIA mouse model phenotypic characterization. The MPS IIIA mouse provides an excellent model for evaluating pathogenic mechanisms of disease and for testing treatment strategies, including enzyme or cell replacement and gene therapy.

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References

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