title: p27(Kip1) deficiency causes organ of Corti pathology and hearing loss.
abstract: p27(Kip1) (p27) has been shown to inhibit several cyclin-dependent kinase molecules and to play a central role in regulating entry into the cell cycle. Once hair cells in the cochlea are formed, p27 is expressed in non-sensory cells of the organ of Corti and prevents their re-entry into the cell cycle. In one line of p27 deficient mice (p27(-/-)), cell division in the organ of Corti continues past its normal embryonic time, leading to continual production of cells in the organ of Corti. Here we report on the structure and function of the inner ear in another line of p27 deficient mice originating from the Memorial Sloan-Kettering Cancer Center. The deficiency in p27 expression of these mice is incomplete, as they retain expression of amino acids 52-197. We determined that mice homozygote for this mutation had severe hearing loss and their organ of Corti exhibited an increase in the number of inner and outer hair cells. There also was a marked increase in the number of supporting cells, with severe pathologies in pillar cells. These data show similarities between this p27(Kip1) mutation and another, previously reported null allele of this gene, and suggest that reducing the inhibition on the cell cycle in the organ of Corti leads to pathology and dysfunction. Manipulations to regulate the time and place of p27 inhibition will be necessary for inducing functionally useful hair cell regeneration.
authors.affiliation: Kresge Hearing Research Institute, The University of Michigan Medical School, MSRB III Room-9303, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0648, USA.
authors.forename: Sho
authors.initials: S
authors.lastname: Kanzaki
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Beyer
authors.forename: Donald L
authors.initials: DL
authors.lastname: Swiderski
authors.forename: Masahiko
authors.initials: M
authors.lastname: Izumikawa
authors.forename: Timo
authors.initials: T
authors.lastname: Stöver
authors.forename: Kohei
authors.initials: K
authors.lastname: Kawamoto
authors.forename: Yehoash
authors.initials: Y
authors.lastname: Raphael
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D015834:Cochlear Diseases / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D006198:Hair Cells, Auditory / Q000000981:diagnostic imaging / Q000473:pathology; D034381:Hearing Loss / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D051379:Mice; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D009925:Organ of Corti / Q000473:pathology*; D016133:Polymerase Chain Reaction; D014463:Ultrasonography
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27