L1 KNOCKOUT MICE SHOW DILATED VENTRICLES, VERMIS HYPOPLASIA AND IMPAIRED EXPLORATION PATTERNS

L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the hum an L1 gene give rise to a complex clinical picture, with mental retard ation, neurologic abnormalities and a variable degree of hydrocephalus , Recently, a transgenic mouse model with a targeted null mutation in the L1 gene was generated, These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of th ese KO mice including magnetic resonance imaging of the brain, neuropa thological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and th e 4th ventricle, and an altered shape of the Sylvius aqueduct, Additio nally, the cerebellar vermis of the KO mice is hypoplastic. Their expl oratory behavior is characterized by stereotype peripheral circling re miniscent of that of rodents with induced cerebellar lesions.