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- Title
Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d.
- Authors
Chen, Ping; Zindy, Frederique; Abdala, Caroline; Liu, Feng; Li, Xiankui; Roussel, Martine F.; Segil, Neil
- Abstract
Maintenance of the post-mitotic state in the post-natal mammalian brain is an active process that requires the cyclin-dependent kinase inhibitors (CKIs) p19[SUPInk4d](Ink4d) and p27[SUPKip1] (Kip1)[SUP1]. In animals with targeted deletions of bothInk4d andKip1, terminally differentiated, post-mitotic neurons are observed to re-enter the cell cycle, divide and undergo apoptosis. However, when either Ink4d or Kip1 alone are deleted, the post-mitotic state is maintained, suggesting a redundant role for these genes in mature neurons[SUP1]. In the organ of Corti -- the auditory sensory epithelium of mammals -- sensory hair cells and supporting cells become post-mitotic during embryogenesis[SUP2] and remain quiescent for the life of the animal. When lost as a result of environmental insult or genetic abnormality, hair cells do not regenerate, and this loss is a common cause of deafness in humans[SUP3]. Here, we report that targeted deletion ofInk4d alone is sufficient to disrupt the maintenance of the post-mitotic state of sensory hair cells in post-natal mice. In Ink4d[SUP-/-] animals, hair cells are observed to aberrantly re-enter the cell cycle and subsequently undergo apoptosis, resulting in progressive hearing loss. Our results identify a novel mechanism underlying a non-syndromic form of progressive hearing loss in mice.
- Subjects
DEAFNESS in animals; CYCLIN-dependent kinases; MICE
- Publication
Nature Cell Biology, 2003, Vol 5, Issue 5, p422
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb976