Gene knockouts of c-src, transforming growth factor beta 1, and tenascin suggest superfluous, nonfunctional expression of proteins.

H~ technology of gene targeting is still in its infancy, but one astonishing theme is being seen over and over. Disruption of a supposedly important gene frequently produces a minimal phenotype. In some cases a phenotype is discovered in an unexpected tissue, but there is no disruption of the tissues where the protein is most highly expressed, and where its function was thought to be most important. A frequent explanation is that proteins are redundant, in the sense that closely related proteins with duplicated functions might fill in for the one eliminated. However, the word redundant can also be used to mean superfluous, and this may be the more appropriate sense. Coexpression of proteins with duplicated functions is probably superfluous and wasteful but, as argued below, may be tolerated. The more extreme view of superfluous expression is that proteins may be prominently expressed in cells or tissues where they have no function at all. Over the last decade many proteins have been discovered through cloning or antibodies, leaving the investigators to determine the function. The search for function frequently begins with immunocytochemistry, to determine where and when the protein is expressed. The interpretation, that the protein is playing an important role at the sites where it is most prominently expressed, is almost universal. If, however, proteins are expressed superfluously, where they have no function, these interpretations need to be re-evaluated.