Modifiable gene expression in mice: kidney-specific deletion of a target gene via the cre-loxP system.
With the advent of gene-targeting in mouse embryonic stem (ES) cells, the use of knockout mice to study the physiological effects of loss of gene function has become increasingly prevalent. However, there are several drawbacks with conventional gene-targeting approaches which may make phenotyping of the resultant mice difficult, if not, impossible. Conventional gene-targeting results in the loss of function of the targeted gene in all cells and tissues, which can be problematic for genes which are required developmentally, which exhibit a wide tissue-specific expression pattern, or are part of complex paracrine systems. As with mice that lack the angiotensinogen or endothelin-1 gene, loss of gene function may lead to a lethal phenotype which can be manifested during embryonic development, at birth or postnatally. These limitations could potentially be circumvented by using a system in which the loss of gene function is placed under spatial and/or temporal control. We will discuss how the cre-loxP recombinase system can be applied to delete a gene in a tissue- and developmentally regulated fashion.
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Departments of Internal Medicine and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa, USA.
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D000818:Animals; D004247:DNA / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression / Q000502:physiology*; D018390:Gene Targeting; D019426:Integrases / Q000235:genetics; D007668:Kidney / Q000502:physiology*; D051379:Mice / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics; D019076:Transgenes / Q000235:genetics*; D014764:Viral Proteins
D014764:Viral Proteins; D004247:DNA; C045073:Cre recombinase; D019426:Integrases