Impaired learning and motor behavior in heterozygous Pafah1b1 (Lis1) mutant mice

Richard Paylor, Shinji Hirotsune, Michael J. Gambello, Lisa Yuva-Paylor, Jacqueline Crawley, Anthony Wynshaw-Boris

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Heterozygous mutation or deletion of Pafah1b1 (LIS1) in humans is associated with syndromes with type 1 lissencephaly, a severe brain developmental disorder resulting from abnormal neuronal migration. We have created Lis1 heterozygous mutant mice by gene targeting. Heterozygous mutant mice are viable and fertile, but display global organizational brain defects as a result of impaired neuronal migration. To assess the functional impact of the mutation, Lis1 heterozygous mice and their wild-type littermates were evaluated on a wide variety of behavioral tests. Lis1 mutant mice displayed abnormal hindpaw clutching responses and were impaired on a rotarod test. Lis1 heterozygous mice were also impaired in the spatial learning version of the Morris water task. Impaired motor behavior and spatial learning and memory in Lis1 mutant mice indicates that impaired neuronal migration can have functional effects on complex behavioral responses. The behavioral findings also support the use of the Lis1 mutant mice as a model from human type 1 lissencephaly.

Original languageEnglish (US)
Pages (from-to)521-537
Number of pages17
JournalLearning and Memory
Issue number5
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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