Unintentional miRNA Ablation Is a Risk Factor in Gene Knockout Studies: A Short Report

One of the most powerful techniques for studying the function of a gene is to disrupt the expression of that gene using genetic engineering strategies such as targeted recombination or viral integration of gene trap cassettes. The tremendous utility of these tools was recognized this year with the a...

Full description

Bibliographic Details
Main Authors:	Osokine, Ivan, Hsu, Ruby, Loeb, Gabriel B, McManus, Michael T
Format:	Online
Language:	English
Published:	Public Library of Science 2008
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2242815/

id	pubmed-2242815
recordtype	oai_dc
spelling	pubmed-22428152008-02-15 Unintentional miRNA Ablation Is a Risk Factor in Gene Knockout Studies: A Short Report Osokine, Ivan Hsu, Ruby Loeb, Gabriel B McManus, Michael T Research Article One of the most powerful techniques for studying the function of a gene is to disrupt the expression of that gene using genetic engineering strategies such as targeted recombination or viral integration of gene trap cassettes. The tremendous utility of these tools was recognized this year with the awarding of the Nobel Prize in Physiology or Medicine to Capecchi, Evans, and Smithies for their pioneering work in targeted recombination mutagenesis in mammals. Another noteworthy discovery made nearly a decade ago was the identification of a novel class of non-coding genes called microRNAs. MicroRNAs are among the largest known classes of regulatory elements with more than 1000 predicted to exist in the mouse genome. Over 50% of known microRNAs are located within introns of coding genes. Given that currently about half of the genes in mouse have been knocked out, we investigated the possibility that intronic microRNAs may have been coincidentally deleted or disrupted in some of these mouse models. We searched published murine knockout studies and gene trap embryonic stem cell line databases for cases where a microRNA was located within or near the manipulated genomic loci, finding almost 200 cases where microRNA expression may have been disrupted along with another gene. Our results draw attention to the need for careful planning in future knockout studies to minimize the unintentional disruption of microRNAs. These data also raise the possibility that many knockout studies may need to be reexamined to determine if loss of a microRNA contributes to the phenotypic consequences attributed to loss of a protein-encoding gene. Public Library of Science 2008-02-15 /pmc/articles/PMC2242815/ /pubmed/18282110 http://dx.doi.org/10.1371/journal.pgen.0040034 Text en © 2008 Osokine et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Osokine, Ivan Hsu, Ruby Loeb, Gabriel B McManus, Michael T
spellingShingle	Osokine, Ivan Hsu, Ruby Loeb, Gabriel B McManus, Michael T Unintentional miRNA Ablation Is a Risk Factor in Gene Knockout Studies: A Short Report
author_facet	Osokine, Ivan Hsu, Ruby Loeb, Gabriel B McManus, Michael T
author_sort	Osokine, Ivan
title	Unintentional miRNA Ablation Is a Risk Factor in Gene Knockout Studies: A Short Report
title_short	Unintentional miRNA Ablation Is a Risk Factor in Gene Knockout Studies: A Short Report
title_full	Unintentional miRNA Ablation Is a Risk Factor in Gene Knockout Studies: A Short Report
title_fullStr	Unintentional miRNA Ablation Is a Risk Factor in Gene Knockout Studies: A Short Report
title_full_unstemmed	Unintentional miRNA Ablation Is a Risk Factor in Gene Knockout Studies: A Short Report
title_sort	unintentional mirna ablation is a risk factor in gene knockout studies: a short report
description	One of the most powerful techniques for studying the function of a gene is to disrupt the expression of that gene using genetic engineering strategies such as targeted recombination or viral integration of gene trap cassettes. The tremendous utility of these tools was recognized this year with the awarding of the Nobel Prize in Physiology or Medicine to Capecchi, Evans, and Smithies for their pioneering work in targeted recombination mutagenesis in mammals. Another noteworthy discovery made nearly a decade ago was the identification of a novel class of non-coding genes called microRNAs. MicroRNAs are among the largest known classes of regulatory elements with more than 1000 predicted to exist in the mouse genome. Over 50% of known microRNAs are located within introns of coding genes. Given that currently about half of the genes in mouse have been knocked out, we investigated the possibility that intronic microRNAs may have been coincidentally deleted or disrupted in some of these mouse models. We searched published murine knockout studies and gene trap embryonic stem cell line databases for cases where a microRNA was located within or near the manipulated genomic loci, finding almost 200 cases where microRNA expression may have been disrupted along with another gene. Our results draw attention to the need for careful planning in future knockout studies to minimize the unintentional disruption of microRNAs. These data also raise the possibility that many knockout studies may need to be reexamined to determine if loss of a microRNA contributes to the phenotypic consequences attributed to loss of a protein-encoding gene.
publisher	Public Library of Science
publishDate	2008
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2242815/
_version_	1611439016702377984

Unintentional miRNA Ablation Is a Risk Factor in Gene Knockout Studies: A Short Report

Similar Items