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Articles, Development/Plasticity/Repair

Mature Mice Lacking Rbl2/p130 Gene Have Supernumerary Inner Ear Hair Cells and Supporting Cells

Sonia M. Rocha-Sanchez, Laura R. Scheetz, Melissa Contreras, Michael D. Weston, Megan Korte, JoAnn McGee and Edward J. Walsh
Journal of Neuroscience 15 June 2011, 31 (24) 8883-8893; DOI: https://doi.org/10.1523/JNEUROSCI.5821-10.2011
Sonia M. Rocha-Sanchez
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Laura R. Scheetz
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Melissa Contreras
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Michael D. Weston
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Megan Korte
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JoAnn McGee
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Edward J. Walsh
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Abstract

Adult mammalian auditory hair cells (HCs) and their associated supporting cells (SCs) do not proliferate, and HC death leads to irreversible neurosensory hearing loss and balance impairment. In nonmammalian vertebrates, loss of HCs induces mitotic proliferation of adjacent nonsensory SCs and/or direct SC transdifferentiation to generate replacement cells. This results in the structural and functional recovery of the nonmammalian sensory systems. Potential replacement of mammalian auditory HCs, either by transplanting cells or by transforming existing cells through molecular therapy, has long been proposed. However, HC replacement strategies with clear therapeutic potential remain elusive. The retinoblastoma (pRB) family of cell cycle regulators, Rb1, Rbl1 (p107), and Rbl2 (p130), regulate the G1- to S-phase transition in proliferating cells. In the inner ear, the biochemical and molecular pathways involving pRBs, particularly p107 and p130, are relatively unexplored and their therapeutic suitability is yet to be determined. In this study, we analyzed the cochleae of adult p130 knock-out (p130−/−) mice and showed that lack of the p130 gene results in extra rows of HCs and SCs in the more apical regions of the cochlea. No evidence of transdifferentiation of these supernumerary SCs into HCs was observed in the p130−/− mouse. Nevertheless, unscheduled proliferation of SCs in the adult p130−/− cochlea coupled to downregulation of bona fide cell cycle inhibitors provides a mechanistic basis for the role of p130 as a regulator of SC and HC mitotic quiescence in the more apical regions of the cochlea. Interestingly, p130−/− mice exhibited nearly normal peripheral auditory sensitivity.

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The Journal of Neuroscience: 31 (24)
Journal of Neuroscience
Vol. 31, Issue 24
15 Jun 2011
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Mature Mice Lacking Rbl2/p130 Gene Have Supernumerary Inner Ear Hair Cells and Supporting Cells
Sonia M. Rocha-Sanchez, Laura R. Scheetz, Melissa Contreras, Michael D. Weston, Megan Korte, JoAnn McGee, Edward J. Walsh
Journal of Neuroscience 15 June 2011, 31 (24) 8883-8893; DOI: 10.1523/JNEUROSCI.5821-10.2011

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Mature Mice Lacking Rbl2/p130 Gene Have Supernumerary Inner Ear Hair Cells and Supporting Cells
Sonia M. Rocha-Sanchez, Laura R. Scheetz, Melissa Contreras, Michael D. Weston, Megan Korte, JoAnn McGee, Edward J. Walsh
Journal of Neuroscience 15 June 2011, 31 (24) 8883-8893; DOI: 10.1523/JNEUROSCI.5821-10.2011
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