Behavioral consequences of bone marrow transplantation in the treatment of murine mucopolysaccharidosis type VII.

The gusmps/gusmps mouse is a model of the human lysosomal storage disease mucopolysaccharidosis type VII caused by deficient beta-glucuronidase activity. Bone marrow transplantation has been shown to correct some of their biochemical and pathological abnormalities but its efficacy in correcting their neurological functional deficits is unknown. We transplanted the neonatal gusmps/gusmps mice and their normal controls and evaluated their central nervous system function with two behavioral tests: the grooming test, a developmentally regulated and genetically 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 strategies to locate the platform in unfamiliar locations. The performance of both normal and mutant transplanted groups was clearly inferior to the untreated normals and, in some instances, close to or worse than the untreated mutants, even though the enzyme abnormalities of the mutants have been partially corrected. Hence, the behavioral deficits in the mutant mice were not restored to normal while similarly treated normal mice showed significant functional deterioration, indicating the detrimental consequence of this therapy in the neonatal period.

Behavioural abnormalities in a murine model of a human lysosomal storage disease.

The gusmps/gusmps mouse is a model of the human lysosomal storage disease mucopolysaccharidosis type VII due to deficient beta-glucuronidase activity. We now report behavioural abnormalities associated with this single gene defect. In grooming, a developmentally regulated and genetically based activity, the mutant mice spent 1-5% of the normal time for body grooming and about 60% of the normal time in face grooming when stimulated with a light water mist. In the Morris water maze which tests spatial learning, the mutants could learn to locate an invisible platform but were deficient in remembering its location the next day or developing strategies to locate it in new positions. Thus, the gusmps/gusmps mouse demonstrates behavioural, memory and cognitive deficiencies suitable for monitoring functional restorations in therapy.