Fig. 5.

Temporal control of astroglia-specific gene deletion in TgN(GFAP-CreERT2) mice by tamoxifen. (A) Principles of inducible gene recombination. Astrocytes of TgN(GFAP-CreERT2) mice express a fusion protein (CreERT2) of the DNA recombinase Cre and a mutated ligand binding domain of the oestrogen receptor. Under normal conditions CreERT2 is trapped in the cytoplasm by binding to heat shock proteins. The oestrogen receptor antagonist tamoxifen can liberate CreERT2 from this complex. After subsequent translocation into the nucleus, CreERT2 selectively excises DNA regions, which were flanked by loxP sites. (B) In cross-breeds of GFAP-CreERT2 mice with appropriate lacZ reporter mice widespread gene recombination in astrocytes can be achieved. The highest recombination rates are observed in the cerebellum (cb) and midbrain (mb). bulbus olfactorius (bo), brainstem (bs), corpus callosum (cc), cortex (cx), hippocampus (hc), hypothalamus (hy), and thalamus (th). Modified from Hirrlinger et al. (2006).