17b-Estradiol (E 2 ) was shown to exert neuroprotective effects both in in vitro and in vivo models of stroke. Although these effects of E 2 are known to require estrogen receptor-a (ERa), the cellular target of estrogen-mediated neuroprotection remains unknown. Using cell type-specific ER mutant mice in an in vivo model of stroke, we specifically investigated the role of ERa in neuronal cells versus its role in the microglia in the mediation of neuroprotection by estrogens. We generated and analyzed two different tissue-specific knockout mouse lines lacking ERa either in cells of myeloid lineage, including microglia, or in the neurons of the forebrain. Both E 2 -treated and E 2 -untreated mutant and control mice were subjected to a permanent middle cerebral artery occlusion for 48 h, and the infarct volume was quantified. Although the infarct volume of E 2 -treated female myeloid-specific ERa knockout mice was similar to that of E 2 -treated control mice, both male and female neuron-specific ERa mutant mice had larger infarcts than did control mice after E 2 treatment. We conclude that neuronal ERa in female and male mice mediates neuroprotective estrogen effects in an in vivo mouse model of stroke, whereas microglial ERa is dispensable.

About 5% to 10% of human gastric tumors harbor oncogenic mutations in the KRAS pathway, but their presence alone is often insufficient for inducing gastric tumorigenesis, suggesting a requirement for additional mutagenic events or microenvironmental stimuli, including inflammation. Assessing the contribution of such events in preclinical mouse models requires Cre recombinase-mediated conditional gene expression in stem or progenitor cells of normal and transformed gastric epithelium. We therefore constructed a bacterial artificial chromosome containing transgene (Tg), comprising the regulatory elements of the trefoil factor 1 (Tff1) gene and the tamoxifen-inducible Cre recombinase (CreERT2)-coding sequence. The resulting Tg (Tff1-CreERT2) mice were crossed with mice harboring conditional oncogenic mutations in Kras or Braf. The administration of tamoxifen to the resulting adult Tg(Tff1-CreERT2);Kras LSL-G12D/þ and Tg(Tff1-CreERT2);Braf LSL-V600E/þ mice resulted in gastric metaplasia, inflammation, and adenoma development, characterized by excessive STAT3 activity. To assess the contribution of STAT3 to the spontaneously developing gastric adenomas in gp130