L1 Knockout Mice Show Dilated Ventricles, Vermis Hypoplasia and Impaired Exploration Patterns

• Published in: Human molecular genetics Vol. 7; no. 6; pp. 999 - 1009
• Main Authors: Fransen, Erik, D'Hooge, Rudi, Van Camp, Guy, Verhoye, Marleen, Sijbers, Jan, Reyniers, Edwin, Soriano, Philippe, Kamiguchi, Hiroyuki, Willemsen, Rob, Koekkoek, Sebastiaan K. E., De Zeeuw, Chris I., De Deyn, Peter P., Van der Linden, Annemie, Lemmon, Vance, Kooy, R. Frank, Willems, Patrick J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.1998
• Subjects: Animals; Behavior, Animal; Biological and medical sciences; Brain Diseases - genetics; Brain Diseases - pathology; Cell Adhesion Molecules, Neuronal - genetics; Cell Adhesion Molecules, Neuronal - physiology; Cerebellum - pathology; Cerebral Ventricles - pathology; Cognition Disorders - genetics; Disease Models, Animal; Humans; Hydrocephalus - genetics; Hydrocephalus - pathology; Leukocyte L1 Antigen Complex; Magnetic Resonance Imaging; Medical genetics; Medical sciences; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Memory Disorders - genetics; Mental and behavioral disorders; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurites; Neurologic Examination; Polymerase Chain Reaction; Hypoplasia; Animal model; Nervous system diseases; Neural cell adhesion molecule; Targeting; Exploratory behavior; Rodentia; Cell adhesion molecule; Congenital disease; Vermis; Vertebrata; Phenotype; Mammalia; Gene; Mouse; CRASH syndrome; Central nervous system disease; Mutation
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/7.6.999

L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the human L1 gene give 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 was generated. These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of these KO mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is characterized by stereotype peripheral circling reminiscent of that of rodents with induced cerebellar lesions.