In order to evaluate the mechanisms leading to neuropathology in Mucopolysaccharidosis type IIIA (MPS-IIIA, Sanfilippo syndrome), we have harvested and cultured primary neural cells isolated from the cerebellum of newborn and adult MPS-IIIA and unaffected mice. Cell viability and plating efficiency were comparable for brain tissue obtained from either newborn or adult MPS-IIIA and unaffected mice. Cultures (newborn and adult) comprised a mixed brain cell population including astrocytes, oligodendrocytes, and neurons. Newborn MPS-IIIA cells contained inclusions and vacuoles consistent with the pathology present in affected brain tissue. Newborn and adult MPS-IIIA brain cells had approximately 5-7% of the sulfamidase activity present in primary neural cells cultured from unaffected newborn and adult mice. In addition, high levels of glucosamine-N-sulfate[α-1,4]hexuronic acid, a heparan sulfate-derived disaccharide, were detected in both newborn and adult MPS-IIIA brain cells. These results suggest that the primary MPS-IIIA brain cells exhibit characteristics of MPS-IIIA phenotype at the histopathological and biochemical level in culture.
- Brain cell culture
- Heparan sulfate
- Lysosomal storage disorder
- Mouse model
- Mucopolysaccharidosis type IIIA