BEHAVIORAL CONSEQUENCES OF BONE-MARROW TRANSPLANTATION IN THE TREATMENT OF MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII

The gus(mps)/gus(mps) mouse is a model of the human lysosomal storage disease mucopolysaccharidosis type VII caused by deficient beta-glucur onidase activity. Bone marrow transplantation has been shown to correc t some of their biochemical and pathological abnormalities but its eff icacy in correcting their neurological functional deficits is unknown. We transplanted the neonatal gus(mps)/gus(mps) mice and their normal controls and evaluated their central nervous system function with two behavioral tests: the grooming test, a developmentally regulated and g enetically based activity, and a Morris water maze test which assessed spatial learning abilities. The two transplanted groups groomed less than the normals, were unable to remember the location of an invisible platform from day to day, and were severely impaired at developing st rategies to locate the platform in unfamiliar locations. The performan ce of both normal and mutant transplanted groups was clearly inferior to the untreated normals and, in some instances, close to or worse tha n the untreated mutants, even though the enzyme abnormalities of the m utants have been partially corrected. Hence, the behavioral deficits i n the mutant mice were not restored to normal while similarly treated normal mice showed significant functional deterioration, indicating th e detrimental consequence of this therapy in the neonatal period.