In situ hybridization studies have revealed that the epidermal growth factor receptor (EGFR/ErbB1) and ErbB2 are expressed in astrocytes . After non-detection of ErbB receptors in astrocytes of the adult brain by immunostaining, we generated Mlc1-tTA;TRE-dnEGFR (Mlc1-dnEGFR) bi-transgenic mice by crossing Mlc1-tTA mice with TRE-dnEGFR mice to investigate the existence of functional ErbB signaling in mature astrocytes. The Mlc1 gene encodes megalencephalic leukoencephalopathy with subcortical cysts-1 (Mlc1), a membrane protein expressed specifically in GFAP-positive cells in the adult brain . Thus, in our transgenic mice, the Mlc1 promoter drove the expression of tetracycline-controlled transactivator (tTA) in astrocytes to activate tetracycline-responsive element (TRE)-controlled transcription through a ‘Tet-off’ system .