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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Multivariate neurocognitive and emotional profile of a mannosidosis murine model for therapy assessment.

alpha-Mannosidosis is a lysosomal storage disorder caused by lysosomal alpha-mannosidase ( LAMAN) deficiency that leads to neurocognitive dysfunctions, psychotic symptoms and emotional changes in human patients. A murine mannosidosis model, LAMAN-deficient mice, was examined on a behavioral task battery that included test for neuromotor, exploratory and neurocognitive (spatial learning and memory) abilities, and multivariate statistical analyses were used to identify behavioral and neurocognitive domains that are most heavily affected by LAMAN deficiency. In addition, we further investigated synaptic plasticity recordings on hippocampal slices that may relate to these behavioral alterations. Correlation analysis revealed significant intra- and intertask correlations and factor analysis that included all 21 behavioral variables identified three main factors (exploration/emotionality, locomotion and learning/memory abilities). Significant correlations were observed between genotype, and factor 1 (exploration/emotionality) and factor 3 (learning/memory abilities). Discriminant function analysis showed that "path length in the open field test" and "time spent in the target quadrant during the water maze probe trial" were the most decisive variables to distinguish between the genotypes. We therefore suggest that these variables would be especially important in forthcoming therapy assessment experiments using this murine mannosidosis model. LAMAN-deficient mice displayed severe changes in synaptic plasticity, which may have contributed to the neurocognitive impairments observed. The present report further shows that targeted deletion of the LAMAN gene in mice mimics many aspects of human alpha-mannosidosis, and these data provide a basis for future therapeutic experiments.[1]

References

  1. Multivariate neurocognitive and emotional profile of a mannosidosis murine model for therapy assessment. Caeyenberghs, K., Balschun, D., Roces, D.P., Schwake, M., Saftig, P., D'Hooge, R. Neurobiol. Dis. (2006) [Pubmed]
 
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