Interpretation of phenotype in genetically engineered mice.
OBJECTIVE
In mice, genetic engineering involves two general approaches-addition of an exogenous gene, resulting in transgenic mice, and use of knockout mice, which have a targeted mutation of an endogenous gene. The advantages of these approaches is that questions can be asked about the function of a particular gene in a living mammalian organism, taking into account interactions among cells, tissues, and organs under normal, disease, injury, and stress situations.


METHODS
Review of the literature concentrating principally on knockout mice and questions of unexpected phenotypes, lack of phenotype, redundancy, and effect of genetic background on phenotype will be discussed.


CONCLUSIONS
There is little gene redundancy in mammals; knockout phenotypes exist even if none are immediately apparent; and investigating phenotypes in colonies of mixed genetic background may reveal not only more phenotypes, but also may lead to better understanding of the molecular or cellular mechanism underlying the phenotype and to discovery of modifier gene(s).
Doetschman
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Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Ohio, USA.
D000818:Animals; D005818:Genetic Engineering; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008822:Mice, Transgenic / Q000235:genetics; D010641:Phenotype; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000235:genetics
D016212:Transforming Growth Factor beta