Figure 1.

Generation and characterization of conditional Tg1/Tg2 transgenic mice. a, Transgenic mice that overexpress Reelin were based on the Tet-off regulated binary system: the Tg1 transgene contains the tTA transactivator set under the control of pCaMKIIα, while the Tg2 transgene contains rlM controlled by the tetO promoter. Double transgenic mice (Tg1/Tg2) express Reelin in neurons expressing CaMKIIα; transgene expression can be switched off by doxycycline administration, which inactivates tTA transactivator. b, Western blot experiments showing Reelin, Dab1, and actin protein levels in protein lysates obtained from control and Tg1/Tg2 adult hippocampus (HP), cerebral cortex (CX), and striatum (STR). Reelin levels are increased in Tg1/Tg2 (T) mice compared with control littermates (C) or reeler animals (R). Dab1 levels are slightly reduced in Tg1/Tg2 mice. c, Immunohistochemical detection of Reelin shows that expression of this protein in control adult mice is restricted to a subset of interneurons distributed throughout the cortex and hippocampal layers, while the striatum shows a diffuse staining (top). In Tg1/Tg2 mice, overexpression of Reelin is observed in hippocampal pyramidal cells and in granule cells of the dentate gyrus (arrows in bottom left panel); Reelin is also expressed in neocortical pyramidal cells (bottom middle) and in striatal neurons (bottom right). I–VI, Cortical layers; CA1–CA3, hippocampal regions; CPu, caudate–putamen nucleus; DOX, doxycycline; H, hilus; LV, lateral ventricle; ML, molecular layer; SP, stratum pyramidale; WM, white matter. Scale bars: c (left): 200 μm; c (middle and right): 100 μm.