L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns

L1 is a neural cell adhesion molecule mainly involved in axon guidance andneuronal migration during brain development. Mutations in the human L1 genegive rise to a complex clinical picture, with mental retardation,neurologic abnormalities and a variable degree of hydrocephalus. Recently,a transgenic mouse model with a targeted null mutation in the L1 gene wasgenerated. These knockout (KO) mice show hypoplasia of the corticospinaltract. Here we have performed further studies of these KO mice includingmagnetic resonance imaging of the brain, neuropathological analysis andbehavioral testing. The ventricular system was shown to be abnormal withdilatation of the lateral ventricles and the 4th ventricle, and an alteredshape of the Sylvius aqueduct. Additionally, the cerebellar vermis of theKO mice is hypoplastic. Their exploratory behavior is characterized bystereotype peripheral circling reminiscent of that of rodents with inducedcerebellar lesions.