Cre recombination could result in excision, inversion or translocation of the floxed genomic GDC-0449 regions depending on the locations and orientations of the loxP elements. By utilization of a specific promoter driving a spatially restricted Cre expression, conditional deletion of a gene or activation of transgene expression can be achieved in specific tissue in mice, thus offering the opportunity to study gene function with spatial control. A further refinement of the Cre/loxP technology is the development of inducible Cre transgene which permits temporal control of gene recombination, allowing investigation of gene functions in a particular developmental stage of the entire life-span of mice. The inducible Cre recombinase is consisted of mutated ligandbinding domain of the mouse estrogen or progesterone receptor and Cre recombinase. The mutated LBD fails to bind to estrogen or progesterone, but retains its ability in binding to synthetic ligands such as tamoxifen, 4-OHT and RU486. When ligand is absent, LBD-Cre is bound by HSP90 and retained in the cytoplasm. Upon ligand binding, LBD-Cre translocates into the nucleus and mediates genomic recombination. Therefore, Cre-mediated recombination is induced by the administration of synthetic ligand, allowing a temporal control of the recombination event. The tamoxifen inducible Cre recombinase protein is composed of Cre recombinase and two tamoxifen-binding domains of mutated mouse estrogen receptor a, one at each end of the Cre recombinase, ensuring efficient binding of MerCreMer to tamoxifen and 4- OHT, but at the same time retaining maximal Cre activity. Neural specific enolase is a glycolytic enzyme enolase abundantly but specifically expressed in terminally differentiated neurons and neuroendocrine cells. Transcript of mouse NSE was detectable from E12 onwards, and its expression was correlated with synaptogenesis. The 1.8 kb rat NSE promoter DNA fragment has been shown to drive expression of target genes in brain neurons of the transgenic mice. A NSE-Cre mouse line has been previously generated which exhibited spatially restricted Cre activity in neurons of the central nervous system. However, such mouse line did not allow temporal control of Cre recombination. In this study, we generated transgenic mouse line that expressed tamoxifen inducible Cre activity in neurons. Nutrient limitation, also known as caloric restriction or dietary restriction, can extend both the replicative and chronological lifespan of eukaryotes as diverse as yeast, nematodes, flies, rodents, and primates. These effects are mediated by the conserved nutrient sensing TOR, AKT/Sch9 and RAS/cAMP pathways, and reduced signaling by these pathways can delay aging even if nutrients are present. Yeast mutants with impaired nutrient sensing, such as tor1, sch9, or ras2 mutants, therefore have an extended lifespan, and rapamycin, an inhibitor of the TOR kinase, can extend the lifespan of mice. In the budding yeast Saccharomyces cerevisiae, the nutrient sensing pathways negatively regulate the activity and nuclear localization of the Rim15 protein kinase. Rim15 in turn is thought to activate the transcription factors Gis1, Msn2 and Msn4, which turn on genes that are needed for long term survival. Accordingly, rim15, gis1, msn2 and msn4 mutations are epistatic over tor1, sch9 and ras2 mutations, and reverse the lifespan-extending phenotypes of the latter.