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HC loss is a major cause of deafness in children and the aging population. However, unlike fish and chickens, humans and other mammals cannot spontaneously regenerate damaged HCs. To restore hearing in deaf children and adults, we first developed HC- or supporting cell (SC)-specific, inducible CreER mouse lines and acutely inactivated genes encoding proteins in the Rb pathway (Rb, p27, and p16). We found that acute inactivation of Rb causes cell cycle reentry and cell death in postnatal HCs (Weber et al., PNAS 2008). These studies will provide evidence of hair cell regeneration in mammals and highlight the therapeutic potential for restoration of hearing in deaf people.