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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

Authors

  • Israely I
  • Costa RM
  • Xie CW
  • Silva AJ
  • Kosik KS
  • Liu X

Journal

Current biology : CB

Publication Data

September 21, 2004

Associated Grants

  • Agency: NIA NIH HHS, Id: AG17542
  • Agency: NINDS NIH HHS, Id: NS38489

Mesh Terms

  • 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