Characterization of Behavior and Brain Pathology of B6, Jm8-Nlgn2-R215htm1 Knock-In Mice

  • Chen, Chia-Hsiang (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Schizophrenia is a severe devastating chronic mental disorder with a high genetic component in its etiology. In our previous study, we systemically sequenced all the exons and promoter region of neuroligin-2 (NLGN2) gene in a sample of 584 schizophrenia patients and 549 control subjects from Taiwan. We identified 19 genetic variants, including six rare missense mutations such as R215H (one patient), V510M (two patients), R621H (one patient), A637T (two patients), P800L (one patient and one control) and A819S (one patient and one control). NLGN2 gene encodes an important cell adhesion protein involved in the synaptogenesis of GABAergic neuron, In cellular model study, we have demonstrated that the R215H mutation of the NLGN2 was a loss-of-function mutation that led to impaired GABAergic synaptogenesis and function. Our study suggests that R215H is a pathogenic mutation associated with schizophrenia and our results have been published in Human Molecular Genetics 2011;20(15):3042-3051 (I F=6.677;R/C= 16/165,GENETICS & HEREDITY). Encouraged by this finding, we further successfully generated a B6 strain of NLGN2 R215H knock-in mice in order to establish an animal model of schizophrenia. To achieve this goal, we propose to conduct the following studies in this study. (1) To assess the behavioral phenotypes of the transgenic mice to determine their relationship with the positive symptoms, negative symptoms, and cognitive dysfunction found in patients with schizophrenia. (2) To conduct brain pathological studies of the mice, including immunohistochemistry and Western blot analysis to assess whether the synaptic function is compromised in this animal. (3) To conduct the electrophysiological studies to assess whether the excitatory and inhibitory neurotransmission are impaired in this animal. (4) To assess the effect of currently available antipsychotic drugs on the animals. We hope that through these studies, we can establish the NLGN2 R215H B6 transgenic mice as a useful animal model of schizophrenia, which will increase our knowledge about the pathogenesis of schizophrenia and facilitate the translational research of schizophrenia, including biomarker study, drug target identification, new drug development for better treatment of schizophrenia.

Project IDs

Project ID:PC10408-2515
External Project ID:MOST104-2314-B182-017
Effective start/end date01/08/1531/07/16


  • schizophrenia
  • genetic mutation
  • animal model
  • synapse


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