Gene-targeted mice, derived from embryonic stem cells, are useful tools to
study gene function during development. However, if the inactivation of the
target gene results in embryonic lethality, the postdevelopmental function
of the gene cannot be further studied. The Cre recombinase-loxP (Cre-loxP)
system was developed to overcome this limitation as well as to confine the
inactivation of the target gene in a cell- or tissue-specific manner. This
system allows for the inactivation of the target gene in a single cell typ
e, thereby allowing the analysis of physiological and pathophysiological co
nsequences of the genetic alteration in mature animals. A unique property o
f the insulin gene to be expressed only in pancreatic beta cells has allowe
d using the beta-cell-specific rat insulin promoter (RIP) for Cre recombina
se expression to inactivate gents in beta cells. The RIP has been used to i
nactivate genes in bt ta cells and analysis of these genetically altered mi
ce has provided important information regarding the role of potential trans
cription factors and the receptors in vivo, for regulation of insulin gene
transcription and in the development of beta cells. The Cre-loxP system is
at a relatively early stage of development, and the ability of this techniq
ue to virtually target any gene in any tissue at any stage of development m
akes the study of gene function in a single cell type in vivo an attainable
goal, it is anticipated that the continued experience with this system wil
l provide an important tr,ol to determine the role of the transcription fac
tors involved in insulin gene regulation and islet cell differentiation and
ultimately provide the basis for novel therapy to treat diabetes.