LIS1, a gene mutated in lissencephaly (“smooth brain”) have been investigated mainly in the developing brain. Initial studies demonstrated distinct ataxia and rapid lethality following Lis1 conditional deletion in adult mice. Therefore, our aim was to investigate the postnatal roles of LIS1 and the underlying mechanism. Conditional Lis1 knockout mice studied by MRI pre, and 5 days post, tamoxifen-induced Lis1 deletion, showed increase in T2 and ADC and decrease MTR and FA0, in the lateral ventricles and in brain regions related to motion and auditory functions. These alterations and changes in the Wnt pathway were partially rescued by LiCl treatment.