| First Author | Arakawa Y | Year | 2019 |
| Journal | PLoS One | Volume | 14 |
| Issue | 7 | Pages | e0220389 |
| PubMed ID | 31361772 | Mgi Jnum | J:279706 |
| Mgi Id | MGI:6343263 | Doi | 10.1371/journal.pone.0220389 |
| Citation | Arakawa Y, et al. (2019) Transgenic mice overexpressing miR-137 in the brain show schizophrenia-associated behavioral deficits and transcriptome profiles. PLoS One 14(7):e0220389 |
| abstractText | Schizophrenia is a psychiatric disorder characterized by positive and negative symptoms and cognitive deficits. The exact cause of schizophrenia is still unknown, but substantial evidence indicates that it has a genetic component. Genome wide association studies demonstrate variants within miR-137 host gene are a risk factor for schizophrenia. However, the direct relationship between the pathophysiology of schizophrenia and the dosage of miR-137 remains unclear. Therefore, in this study, we generated transgenic mice overexpressing miR-137 (miR-137 Tg mice) with the neuron-specific Thy-1 promoter and examined schizophrenia-related phenotypes in these mice. Overexpression of miR-137 was observed in various brain regions of the miR-137 Tg mice, with down-regulation of putative miR-137 targets. MiR-137 Tg mice showed sensory gating deficits in a prepulse inhibition test, social deficits in a sociability and social novelty test, and cognitive deficits in a novel object recognition test. Interestingly, the predicted-altered pathways of the medial prefrontal cortex of miR-137 Tg mice were partially overlapped with those of the dorsolateral prefrontal cortex in postmortem brain of patients who died in equal to or less than 4 years after initial diagnosis of schizophrenia in published data. These results suggest that overexpression of miR-137 in the whole brain induces the several phenotypes that are relevant to aspects of psychiatric disorders, such as schizophrenia. Based on these findings, miR-137 Tg mice may have the potential to become a useful tool in researching the pathophysiology of psychiatric disorders. |
