Inducible and reversible silencing of the Pvalb gene in mice: An in vitro and in vivo study. (17th June 2019)

• Record Type: Journal Article
• Authors: Filice, Federica; Blum, Walter; Lauber, Emanuel; Schwaller, Beat
• Is Part Of: European journal of neuroscience. Volume 50:Number 4(2019)
• Page Start: 2694
• Page End: 2706
• Publication Date: 2019-06-17
• Subjects: inducible system autism spectrum disorder -- lentiviral transgenesis -- parvalbumin -- RNA interference; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.14404
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Inducible and reversible regulation of gene expression is a powerful approach for unraveling gene functions. Here, we describe the generation of a system to efficiently downregulate in a reversible and inducible manner the Pvalb gene coding for the calcium‐binding protein parvalbumin (PV) in mice. We made use of an IPTG‐inducible short hairpin RNA to activate Pvalb transcript knockdown and subsequently downregulate PV. The downregulation was rapidly reversed after withdrawal of IPTG. In vitro and in vivo experiments revealed a decrease in PV expression of ≥50% in the presence of IPTG and full reversibility after IPTG removal. We foresee that the tightly regulated and reversible PV downregulation in mice in vivo will provide a new tool for the control of Pvalb transcript expression in a temporal manner. Because PV protein and PVALB transcript levels were found to be lower in the brain of patients with autism spectrum disorder and schizophrenia, the novel transgenic mouse line might serve as a model to investigate the putative role of PV in these neurodevelopmental disorders. Abstract : Modulation of the Pvalb gene through the generation of an inducible/reversible transgenic mouse line. A lentiviral mediated‐transgenesis approach combined with the use of RNAi allows for the temporal control of the Pvalb gene transcript in an inducible and reversible manner.