Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of Corti

Hearing loss is most often the result of hair-cell degeneration due to gene tic abnormalities or ototoxic and traumatic insults. In the postembryonic a nd adult mammalian auditory sensory epithelium, the organ of Corti, no hair -cell regeneration has ever been observed, However, non mammalian hair-cell epithelia are capable of regenerating sensory hair cells as a consequence of nonsensory supporting-cell proliferation. The supporting cells of the or gan of Corti are highly specialized, terminally differentiated cell types t hat apparently are incapable of proliferation. At the molecular level termi nally differentiated tells have been shown to es press high levels of cell- cycle inhibitors, in particular, cyclin-dependent kinase inhibitors [ Parke r, S, B,, Et al, (1995) Science 267, 1024-1027], which are thought to be re sponsible for preventing these cells from reentering the cell cycle. Here w e report that the cyclin-dependent kinase inhibitor p27(Kip1) is selectivel y expressed in the supporting-cell population of the organ of Corti, Effect s of p27(Kip1)-gene disruption include ongoing cell proliferation in postna tal and adult mouse organ of Corti at time points well after mitosis normal ly has ceased during embryonic development. This suggests that release from p27(Kip1)-induced cell-cycle arrest is sufficient to allow supporting-cell proliferation to occur. This finding may provide an important pathway for inducing hair-cell regeneration in the mammalian hearing organ.