title: Heterozygous L1-deficient mice express an autism-like phenotype.
abstract: The L1CAM (L1) gene encodes a cell adhesion molecule that contributes to several important processes in the developing and adult nervous system, including neuronal migration, survival, and plasticity. In humans and mice, mutations in the X chromosome-linked gene L1 cause severe neurological defects in males. L1 heterozygous female mice with one functional copy of the L1 gene show complex morphological features that are different from L1 fully-deficient and wild-type littermate mice. However, almost no information is available on the behavior of L1 heterozygous mice and humans. Here, we investigated the behavior of heterozygous female mice in which the L1 gene is constitutively inactivated. These mice were compared to wild-type littermate females. Animals were assessed in five categories of behavioral tests: five tests for anxiety/stress/exploration, four tests for motor abilities, two tests for spatial learning, three tests for social behavior, and three tests for repetitive behavior. We found that L1 heterozygous mice express an autism-like phenotype, comprised of reduced social behaviors and excessive self-grooming (a repetitive behavior also typical in animal models of autism). L1 heterozygous mice also exhibited an increase in sensitivity to light, assessed by a reluctance to enter the lighted areas of novel environments. However, levels of anxiety, stress, motor abilities, and spatial learning in L1 heterozygous mice were similar to those of wild-type mice. These observations raise the possibility that using molecules known to trigger L1 functions may become valuable in the treatment of autism in humans.
authors.affiliation: Department of Psychology, Program in Behavioral and Systems Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sauce
authors.affiliation: Department of Psychology, Program in Behavioral and Systems Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Wass
authors.affiliation: Department of Psychology, Program in Behavioral and Systems Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Meera
authors.initials: M
authors.lastname: Netrakanti
authors.affiliation: Department of Psychology, Program in Behavioral and Systems Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Saylor
authors.affiliation: Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: schachner@biology.rutgers.edu.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.affiliation: Department of Psychology, Program in Behavioral and Systems Neuroscience, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: matzel@rci.rutgers.edu.
authors.forename: Louis D
authors.initials: LD
authors.lastname: Matzel
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics* / Q000523:psychology*; D001522:Behavior, Animal; D005260:Female; D006579:Heterozygote; D051379:Mice; D009043:Motor Activity; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics*; D010641:Phenotype; D012919:Social Behavior; D065853:Spatial Learning / Q000502:physiology; D013315:Stress, Psychological / Q000235:genetics
chemical_list: D039842:Neural Cell Adhesion Molecule L1
keywords: Autism; L1CAM; Mice; Social behavior; Spatial learning