Abstract |
Schizophrenia (SCZ) is a severe mental disorder characterized by delusion, hallucination, and cognitive deficits. We have previously identified from schizophrenia patients a loss-of-function mutation Arg215→His215 (R215H) of neuroligin 2 (NLGN2) gene, which encodes a cell adhesion molecule critical for GABAergic synapse formation and function. Here, we generated a novel transgenic mouse line with neuroligin-2 (NL2) R215H mutation. The single point mutation caused a significant loss of NL2 protein in vivo, reduced GABAergic transmission, and impaired hippocampal activation. Importantly, R215H KI mice displayed anxiety-like behavior, impaired pre-pulse inhibition (PPI), cognition deficits and abnormal stress responses, recapitulating several key aspects of schizophrenia-like behaviors. Our results demonstrate a significant impact of a single point mutation NL2 R215H on brain functions, providing a novel animal model for the study of schizophrenia and neuropsychiatric disorders.
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Authors | Dong-Yun Jiang, Zheng Wu, Cody Tieu Forsyth, Yi Hu, Siu-Pok Yee, Gong Chen |
Journal | Molecular brain
(Mol Brain)
Vol. 11
Issue 1
Pg. 31
(06 01 2018)
ISSN: 1756-6606 [Electronic] England |
PMID | 29859117
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cell Adhesion Molecules, Neuronal
- Nerve Tissue Proteins
- neuroligin 2
- gamma-Aminobutyric Acid
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Topics |
- Animals
- Behavior, Animal
- Cell Adhesion Molecules, Neuronal
(genetics)
- Disease Models, Animal
- Hippocampus
(metabolism)
- Humans
- Mice, Transgenic
- Mutation
(genetics)
- Nerve Tissue Proteins
(genetics)
- Neurons
(metabolism)
- Schizophrenia
(genetics, pathology)
- Stress, Physiological
- Synapses
(metabolism)
- Synaptic Transmission
- gamma-Aminobutyric Acid
(metabolism)
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