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Creation and Validation of an Automated Head Twitch Analysis Instrument to Study a Mouse Model of Psychosis

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Serotonin 2A receptor (5-HT2AR) levels are decreased in the brains of schizophrenia patients. This phenomenon is modeled in mice that lack the transcription factor Egr3. The head-twitch response

Serotonin 2A receptor (5-HT2AR) levels are decreased in the brains of schizophrenia patients. This phenomenon is modeled in mice that lack the transcription factor Egr3. The head-twitch response (HTR) is a behavioral assay used to assess the physiological function of 5-HT2ARs. However, current quantification methods are time consuming and prone to inter-rater variability. Here, we demonstrate the validity and reliability of an automated head-twitch system to quantify HTRs of Egr3-/- mice.

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Date Created
  • 2020-05

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Association of SNPs in EGR3 and ARC with Schizophrenia Supports a Biological Pathway for Schizophrenia Risk

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We have previously hypothesized a biological pathway of activity-dependent synaptic plasticity proteins that addresses the dual genetic and environmental contributions to schizophrenia. Accordingly, variations in the immediate early gene EGR3,

We have previously hypothesized a biological pathway of activity-dependent synaptic plasticity proteins that addresses the dual genetic and environmental contributions to schizophrenia. Accordingly, variations in the immediate early gene EGR3, and its target ARC, should influence schizophrenia susceptibility. We used a pooled Next-Generation Sequencing approach to identify variants across these genes in U.S. populations of European (EU) and African (AA) descent. Three EGR3 and one ARC SNP were selected and genotyped for validation, and three SNPs were tested for association in a replication cohort. In the EU group of 386 schizophrenia cases and 150 controls EGR3 SNP rs1877670 and ARC SNP rs35900184 showed significant associations (p = 0.0078 and p = 0.0275, respectively). In the AA group of 185 cases and 50 controls, only the ARC SNP revealed significant association (p = 0.0448). The ARC SNP did not show association in the Han Chinese (CH) population. However, combining the EU, AA, and CH groups revealed a highly significant association of ARC SNP rs35900184 (p = 2.353 x 10[superscript −7]; OR [95% CI] = 1.54 [1.310–1.820]). These findings support previously reported associations between EGR3 and schizophrenia. Moreover, this is the first report associating an ARC SNP with schizophrenia and supports recent large-scale GWAS findings implicating the ARC complex in schizophrenia risk. These results support the need for further investigation of the proposed pathway of environmentally responsive, synaptic plasticity-related, schizophrenia genes.

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Date Created
  • 2015-10-16