The loss-of-function studies revealed that ErbB signaling was specifically required for hypertrophic remodeling of reactive astrocytes. To examine whether ErbB activation in astrocytes was solely responsible for the hypertrophic response, we generated another mouse line with inducible gene expression in astrocytes by crossing Mlc1-tTA with TRE-ErbB2V664E mice. Among ErbB1–4 receptors, ErbB2 does not bind any known ligand but is the preferred partner of other ErbB members . Moreover, dimerization with ErbB2 potentiates the downstream signaling of ErbB receptors . The ectopically expressed gene in TRE-ErbB2V664E transgenic mice encodes an active form of rat ErbB2 (ErbB2V664E) that contains an amino-acid mutation (Vla664/Glu664) within the transmembrane domain that facilitates its dimerization and activation .