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Interpretation of knockout experiments: the congenic footprint
L C Schalkwyk1, C Fernandes, M W Nash
1Social, Genetic and Developmental Psychiatry Centre (PO82), Institute of Psychiatry, King's College London, London, United Kingdom. l.schalkwyk@iop.kcl.ac.uk
Genes, Brain, and Behavior
|March 3, 2007
Summary
Genetic background significantly impacts gene knockout studies. Researchers found expression differences in multiple genes near the knockout locus, highlighting the need for caution when interpreting knockout phenotypes.
Area of Science:
- Genetics
- Genomics
- Molecular Biology
Background:
- Genetic background is crucial in gene targeting experiments.
- Knockout alleles are backcrossed onto standard inbred backgrounds, creating congenic strains.
- Embryonic stem (ES)-cell-derived chromosome segments flanking knockout alleles are often overlooked.
Purpose of the Study:
- To investigate the impact of genetic background on gene knockout phenotypes.
- To identify expression differences in genes surrounding the cholecystokinin 2 (Cckbr) knockout locus.
- To assess the implications of these differences for interpreting knockout study results.
Main Methods:
- Utilized cholecystokinin 2 (Cckbr) knockout mice backcrossed with C57BL/6.
- Analyzed gene expression patterns in the vicinity of the Cckbr locus.
- Quantified expression differences across a 40 Mb genomic region.
Main Results:
- Identified a 'congenic footprint' with expression differences in at least 10 genes near the Cckbr locus.
- Observed expression differences predominantly in the knockout-low direction.
- These expression changes suggest background dependence in knockout phenotypes.
Conclusions:
- Genetic background significantly influences gene knockout phenotypes.
- Caution is needed when attributing phenotypic effects solely to the targeted gene.
- Genetic background offers opportunities to study broader biological system responses to genetic perturbations.
