Transgenic mice overexpressing miR-137 in the brain show schizophrenia-associated behavioral deficits and transcriptome profiles

PloS One
Yuuichi ArakawaMotohisa Suzuki

Abstract

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 afte...Continue Reading

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Citations

Oct 7, 2020·Seminars in Cell & Developmental Biology·Natássia Cristina Martins OliveiraMário Henrique Bengtson

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Methods Mentioned

BETA
PCR
transgenic
RNA-Seq
Chip

Software Mentioned

Correlation Engine
miRWalk
Ingenuity Pathway Analysis ( IPA )
Targetscan6
IPA
SAS

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