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Deletion of the Neuron-Specific Protein Delta-Catenin Leads to Severe Cognitive and Synaptic Dysfunction

2004; Elsevier BV; Volume: 14; Issue: 18 Linguagem: Inglês

10.1016/j.cub.2004.08.065

1879-0445

Inbal Israely, Rui M. Costa, Cui Wei Xie, Alcino J. Silva, Kenneth S. Kosik, Xin Liu,

Neuroscience and Neuropharmacology Research

Abstract Delta-catenin (δ-catenin) is a neuron-specific catenin, which has been implicated in adhesion and dendritic branching [1, 2]. Moreover, deletions of δ-catenin correlate with the severity of mental retardation in Cri-du-Chat syndrome (CDCS), which may account for 1% of all mentally retarded individuals [3]. Interestingly, δ-catenin was first identified through its interaction with Presenilin-1 (PS1), the molecule most frequently mutated in familial Alzheimer's Disease (FAD) [4]. We investigated whether deletion of δ-catenin would be sufficient to cause cognitive dysfunction by generating mice with a targeted mutation of the δ-catenin gene ( δ-cat −/− ). We observed that δ-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 δ-catenin [1, 5], are significantly reduced in mutant mice. These deficits are severe but specific because δ-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 β-catenin. These data reveal a critical role for δ-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.