Neurologic function during developmental and adult stages in Dab1scm (scrambler) mutant mice

Homozygous Dab1scm mouse mutants with cell ectopias in cerebellar cortex, hippocampus, and neocortex were compared to non-ataxic controls on the SHIRPA primary screening battery on postnatal days 8, 15, and 22, as well as in the adult period. Dab1scm mutants were distinguished from non-ataxic controls as early as postnatal day 8 based on body tremor, gait anomalies, and body weight. On postnatal day 15, motor coordination deficits were evident on horizontal bar and inclined or vertical grid tests in association with a weaker grip strength. Likewise, mutants were distinguished from controls on drop righting and hindpaw clasping tests. Further differences were detected on postnatal day 22 in the form of fewer visual placing, touch escape, trunk curl, freezing, and vocalization responses, as well as squares traversed in the open-field. Evaluation at the adult age demonstrated similar impairments, indicative of permanent motor alterations. Neuronal metabolic activity was estimated by cytochrome oxidase histochemistry on cerebellar sections. Cerebellar cortical layers and efferent deep nuclei of Dab1scm mice appeared hypometabolic relative to non-ataxic mice despite normal metabolism in both regular and ectopic Purkinje cells.

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► Dab1scm mutants have ectopias in cerebellum and hippocampus.
► Dab1scm mutants were dissociated from controls for tremor, gait, and body weight on P8.
► Dab1scm mutants were dissociated from controls on motor coordination on P15.
► Evaluation in adults demonstrated permanent impairments in motor control.
► Cerebellar cortex and deep nuclei of Dab1scm mice appeared hypometabolic.