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 s everal 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 ta rgeted gene in all cells and tissues, which can be problematic for gen es which are required developmentally, which exhibit a wide tissue-spe cific expression pattern, or are part of complex paracrine systems. As with mice that lack the angiotensinogen or endothelin-l gene, loss of gene function may lead to a lethal phenotype which can be manifested during embryonic development, at birth or postnatally. These limitatio ns could potentially be circumvented by using a system in which the lo ss of gene function is placed under spatial and/or temporal control. W t: will discuss how the cre-loxP recombinase system can be applied to delete a gene in a tissue- and developmentally regulated fashion.