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Appearances can be deceiving: phenotypes of knockout mice.
Ivana Barbaric1, Gaynor Miller, T Neil Dear
1Department of Biomedical Sciences, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, United Kingdom.
Briefings in Functional Genomics & Proteomics
|June 23, 2007
Summary
Investigating gene function in mammals reveals that some gene knockouts show no obvious phenotype due to biological robustness. This phenomenon, where gene effects are masked, requires careful study in mouse models.
Area of Science:
- Mammalian functional genomics
- Post-genomic era research
Background:
- Gene targeting in embryonic stem cells allows for the creation of knockout mice.
- A proportion of knockout mice exhibit no detectable phenotypic changes.
- Advanced phenotyping reveals subtle or conditional phenotypes, highlighting the need for thorough investigation.
Purpose of the Study:
- To review examples of mouse knockouts supporting the concept of biological robustness.
- To discuss potential evolutionary mechanisms and reasons for biological robustness.
Main Methods:
- Review of existing literature on mouse knockout models and phenotyping studies.
- Analysis of cases where gene inactivation effects were only observed upon secondary gene inactivation.
Main Results:
- Examples of mouse knockouts demonstrate biological robustness, where gene function is masked.
- Phenotypic effects can be subtle, conditional, or revealed only in specific genetic contexts.
- Biological robustness has not been systematically analyzed in mice compared to yeast.
Conclusions:
- Biological robustness is a significant factor in mammalian functional genomics.
- Further systematic analysis of robustness in mouse models is warranted.
- Understanding robustness is crucial for comprehensive gene function elucidation.
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