Deletion of the neuron-specific protein delta-catenin leads to severe cognitive and synaptic dysfunction.
Delta-catenin (delta-catenin) is a neuron-specific catenin, which has been implicated in adhesion and dendritic branching. Moreover, deletions of delta-catenin correlate with the severity of mental retardation in Cri-du-Chat syndrome (CDCS), which may account for 1% of all mentally retarded individuals. Interestingly, delta-catenin was first identified through its interaction with Presenilin-1 (PS1), the molecule most frequently mutated in familial Alzheimer's Disease (FAD). We investigated whether deletion of delta-catenin would be sufficient to cause cognitive dysfunction by generating mice with a targeted mutation of the delta-catenin gene (delta-cat(-/-)). We observed that delta-cat(-/-) animals are viable and have severe impairments in cognitive function. Furthermore, mutant mice display a range of abnormalities in hippocampal short-term and long-term synaptic plasticity. Also, N-cadherin and PSD-95, two proteins that interact with delta-catenin, are significantly reduced in mutant mice. These deficits are severe but specific because delta-cat(-/-) mice display a variety of normal behaviors, exhibit normal baseline synaptic transmission, and have normal levels of the synaptic adherens proteins E-cadherin and beta-catenin. These data reveal a critical role for delta-catenin in brain function and may have important implications for understanding mental retardation syndromes such as Cri-du-Chat and neurodegenerative disorders, such as Alzheimer's disease, that are characterized by cognitive decline.
Pubmed ID: 15380068 RIS Download
Analysis of Variance | Animals | Armadillo Domain Proteins | Cadherins | Catenins | Cell Adhesion Molecules | Cognition Disorders | Conditioning (Psychology) | Cytoskeletal Proteins | Electrophysiology | Fear | Guanylate Kinase | Hippocampus | Immunoprecipitation | Intracellular Signaling Peptides and Proteins | Maze Learning | Membrane Proteins | Mice | Mice, Mutant Strains | Mutation | Nerve Tissue Proteins | Neurodegenerative Diseases | Neuronal Plasticity | Neurons | Phosphoproteins | Psychomotor Performance | Synapses