title: Role of the cytoplasmic domain of the L1 cell adhesion molecule in brain development.
abstract: Mutations in the human L1CAM gene cause X-linked hydrocephalus and MASA (Mental retardation, Aphasia, Shuffling gait, Adducted thumbs) syndrome. In vitro studies have shown that the L1 cytoplasmic domain (L1CD) is involved in L1 trafficking, neurite branching, signaling, and interactions with the cytoskeleton. L1cam knockout (L1(KO)) mice have hydrocephalus, a small cerebellum, hyperfasciculation of corticothalamic tracts, and abnormal peripheral nerves. To explore the function of the L1CD, we made three new mice lines in which different parts of the L1CD have been altered. In all mutant lines L1 protein is expressed and transported into the axon. Interestingly, these new L1CD mutant lines display normal brain morphology. However, the expression of L1 protein in the adult is dramatically reduced in the two L1CD mutant lines that lack the ankyrin-binding region and they show defects in motor function. Therefore, the L1CD is not responsible for the major defects observed in L1(KO) mice, yet it is required for continued L1 protein expression and motor function in the adult.
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Suni
authors.initials: S
authors.lastname: Lee
authors.forename: Candace L
authors.initials: CL
authors.lastname: Haddox
authors.forename: Eli J
authors.initials: EJ
authors.lastname: Weaver
authors.forename: Vance P
authors.initials: VP
authors.lastname: Lemmon
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D001522:Behavior, Animal / Q000502:physiology*; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D018929:Cell Culture Techniques; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology; D009154:Mutation; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000648:ultrastructure; D013037:Spatial Behavior / Q000502:physiology; D013997:Time Factors
chemical_list: D039842:Neural Cell Adhesion Molecule L1