Behavioral defects in lysosomal á-mannosidase deficient mice

K. Caeyenberghs, L. van Aerschot, P. Saftig and R. D’Hooge

Laboratory of Biological Psychology, K.U. Leuven, Leuven, Belgium

Deficiency of á-mannosidase causes the autosomal recessive lysosomal storage disease, á- mannosidosis. Mice with targeted disruption of the lysosomal á-mannosidase gene were generated as the first mouse model for human á-mannosidosis. Performance on tests of motor ability, exploratory activity and learning/memory was assessed in á-mannosidase deficient mice and their wild type littermates at 3 months of age. á-Mannosidase deficient mice showed impaired rotarod motor coordination performance and impaired activity on tests of neuromotor functions. The exploration patterns of á-mannosidase deficient mice were also significantly altered, which could not be explained by higher levels of anxiety. Passive avoidance learning was not impaired in á-mannosidase mice. In the Morris water maze, á-mannosidase deficient mice displayed impaired hidden-platform acquisition performance, and retention deficits during the probe trials. Neuromotor defects, decreased exploratory activity and impaired learning/memory, reported here in á-mannosidase deficient mice, may relate to the decline of neuromotor and cognitive functions in á-mannosidosis patients. á-Mannosidase deficient mice provide a valid model for investigation of new therapeutic strategies for á-mannosidosis, such as enzyme replacement.

Paper presented at Measuring Behavior 2005 , 5^th International Conference on Methods and Techniques in Behavioral Research, 30 August - 2 September 2005, Wageningen, The Netherlands.

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