Espana-Agusti, J., Tuveson, D. A., Adams, D. J., Matakidou, A. (June 2015) A minimally invasive, lentiviral based method for the rapid and sustained genetic manipulation of renal tubules. Sci Rep, 5. p. 11061. ISSN 2045-2322 (Electronic)2045-2322 (Linking)
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Abstract
The accelerated discovery of disease-related genes emerging from genomic studies has strained the capacity of traditional genetically engineered mouse models (GEMMs) to provide in-vivo validation. Direct, somatic, genetic engineering approaches allow for accelerated and flexible genetic manipulation and represent an attractive alternative to GEMMs. In this study we investigated the feasibility, safety and efficiency of a minimally invasive, lentiviral based approach for the sustained in-vivo modification of renal tubular epithelial cells. Using ultrasound guidance, reporter vectors were directly injected into the mouse renal parenchyma. We observed transgene expression confined to the renal cortex (specifically proximal and distal tubules) and sustained beyond 2 months post injection. Furthermore, we demonstrate the ability of this methodology to induce long-term, in-vivo knockdown of candidate genes either through somatic recombination of floxed alleles or by direct delivery of specific shRNA sequences. This study demonstrates that ultrasound-guided injection of lentiviral vectors provides a safe and efficient method for the genetic manipulation of renal tubules, representing a quick and versatile alternative to GEMMs for the functional characterisation of disease-related genes.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders Investigative techniques and equipment organism description > model organism |
| CSHL Authors: | |
| Communities: | CSHL labs > Tuveson lab |
| Depositing User: | Matt Covey |
| Date: | 5 June 2015 |
| Date Deposited: | 10 Jun 2015 19:17 |
| Last Modified: | 09 Nov 2017 21:35 |
| PMCID: | PMC4457145 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/31566 |
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