Schalkwyk, LC and Fernandes, C and Nash, MW and Kurrikoff, K and Vasar, E and Kõks, S (2007) Interpretation of knockout experiments: the congenic footprint. Genes, Brain and Behavior, 6 (3). pp. 299-303. DOI https://doi.org/10.1111/j.1601-183x.2007.00304.x
Schalkwyk, LC and Fernandes, C and Nash, MW and Kurrikoff, K and Vasar, E and Kõks, S (2007) Interpretation of knockout experiments: the congenic footprint. Genes, Brain and Behavior, 6 (3). pp. 299-303. DOI https://doi.org/10.1111/j.1601-183x.2007.00304.x
Schalkwyk, LC and Fernandes, C and Nash, MW and Kurrikoff, K and Vasar, E and Kõks, S (2007) Interpretation of knockout experiments: the congenic footprint. Genes, Brain and Behavior, 6 (3). pp. 299-303. DOI https://doi.org/10.1111/j.1601-183x.2007.00304.x
Abstract
<jats:p> <jats:bold>In gene targeting experiments, the importance of genetic background is now widely appreciated, and knockout alleles are routinely backcrossed onto a standard inbred background. This produces a congenic strain with a substantial segment of embryonic stem (ES)‐cell‐derived chromosome still flanking the knockout allele, a phenomenon often neglected in knockout studies. In cholecystokynin 2 (<jats:italic>Cckbr</jats:italic>) knockout mice backcrossed with C57BL/6, we have found a clear ‘congenic footprint’ of expression differences in at least 10 genes across 40 Mb sequence flanking the <jats:italic>Cckbr</jats:italic> locus, each of which is potentially responsible for aspects of the ‘knockout’ phenotype. The expression differences are overwhelmingly in the knockout‐low direction, which may point to a general phenomenon of background dependence. This finding emphasizes the need for caution in using gene knockouts to attribute phenotypic effects to genes. This is especially the case when the gene is of unknown function or the phenotype is unexpected, and is a particular concern for large‐scale knockout and phenotypic screening programmes. However, the impact of genetic background should not be simply viewed as a potential confound, but as a unique opportunity to study the broader responses of a system to a specific (genetic) perturbation.</jats:bold> </jats:p>
Item Type: | Article |
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Uncontrolled Keywords: | Cckbr; congenic footprint; gene expression; knockout; microarray; mouse mutant |
Subjects: | Q Science > QH Natural history > QH426 Genetics |
Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 17 Dec 2014 19:05 |
Last Modified: | 07 Aug 2024 20:35 |
URI: | http://repository.essex.ac.uk/id/eprint/11103 |
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