GABAergic deficits and schizophrenia-like behaviors in a mouse model carrying patient-derived neuroligin-2 R215H mutation.

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.

• 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)

Chemical References

• Cell Adhesion Molecules, Neuronal
• Nerve Tissue Proteins
• neuroligin 2
• gamma-Aminobutyric Acid

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)