Novel animal models for studying complex brain disorders: BAC-driven miRNA-mediated in vivo silencing of gene expression.

Molecular Psychiatry
K A GarbettK Mirnics

Abstract

In schizophrenia, glutamic acid decarboxylase 1 (GAD1) disturbances are robust, consistently observed, cell-type specific and represent a core feature of the disease. In addition, neuropeptide Y (NPY), which is a phenotypic marker of a sub-population of GAD1-containing interneurons, has shown reduced expression in the prefrontal cortex in subjects with schizophrenia, suggesting that dysfunction of the NPY+ cortical interneuronal sub-population might be a core feature of this devastating disorder. However, modeling gene expression disturbances in schizophrenia in a cell type-specific manner has been extremely challenging. To more closely mimic these molecular and cellular human post-mortem findings, we generated a transgenic mouse in which we downregulated GAD1 mRNA expression specifically in NPY+ neurons. This novel, cell type-specific in vivo system for reducing gene expression uses a bacterial artificial chromosome (BAC) containing the NPY promoter-enhancer elements, the reporter molecule (eGFP) and a modified intron containing a synthetic microRNA (miRNA) targeted to GAD1. The animals of isogenic strains are generated rapidly, providing a new tool for better understanding the molecular disturbances in the GABAergic system ob...Continue Reading

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Citations

Nov 20, 2013·Experimental Cell Research·Sára KálmánKároly Mirnics
Dec 11, 2013·Molecular Psychiatry·M J SchmidtK Mirnics
Jan 28, 2015·Molecular Psychiatry·J A BrownKároly Mirnics
Aug 31, 2010·Biological Psychiatry·Szatmár HorváthKároly Mirnics
Nov 19, 2013·Neurobiology of Disease·Jacquelyn A BrownKároly Mirnics
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May 11, 2012·Developmental Neuroscience·Martin J Schmidt, Karoly Mirnics
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Feb 19, 2021·Brain Research·Allison AndersonKaroly Mirnics
Jul 16, 2017·Journal of Affective Disorders·Yu-Chu Ella ChungPo-Hsiu Kuo

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Methods Mentioned

BETA
transgenic
PCR
fluorescence imaging
transfection
electrophoresis
genotyping
dissection

Software Mentioned

Adobe Photoshop
IPLAb

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