Mouse model for regulation of telomerase

Telomeres provide stabilih to chromosomes, broken chromosome that lack tclomcres undergo fusions, rearrangements and translocalions. Tclomcre sequences often consist of tandem G-nch simple repeats, and are synthesized b the RNP DNA polymerase telomcrase Tclomerase activity has been implicated in cancer progression since most tumor samples have active enzyme while most normal tissues do not We have been using the mouse as a model to stud the regulation of tclomcrase in development and cancer in mammalian cells In the mouse, (elomere length shortens ( I ) and the level of the tolomerase RN A component is don regulated in during development (2). In mouse models of multistage tumor development, telomerasc is activated at late stages in tumor progression (3) To critical) test the Inpothesis that telomerase inhibition and telomcrc shortening ill inhibit tumor growth in vivo, wc have generated a "knockout" mouse that lacks both aileles of the essential mouse tclomerase RNA component. Cells and tissues domed from this mouse lack telomoraso activity We will describe preliminan. studios on the phenotype of the mice and of telomerase null cells derived from these mice.