Impaired motor learning performance in cerebellar En-2 mutant mice.

Mice homozygous for a null mutation in their En-2 gene exhibit cerebellar neuroanatomical alterations including absence and misplacements of specific fissures and size reduction. The present study investigated cerebellar function by comparing the behavior of age-matched homozygous and heterozygous En-2 mutant and wild-type mice. Motor function of the mutants was found normal in several situations. Habituation to novelty in the open field was not significantly different in mutants. However, in a motor learning paradigm, the rotating rod, the performance of homozygous mutant mice improved significantly less than that of the heterozygous mice which were also significantly impaired compared to wild-type mice. Unlike other cerebellar mutants in which severe motor or sensory defects are obvious, the En-2 mouse model offers a unique tool to study the role of cerebellum in complex behavioral phenomena, including motor learning, without confounding effects.