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

Research output: Contribution to journalArticle

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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 p-/-130 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.

Original languageEnglish (US)
Pages (from-to)8883-8893
Number of pages11
JournalJournal of Neuroscience
Volume31
Issue number24
DOIs
StatePublished - Jun 15 2011

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Inner Auditory Hair Cells
Inner Ear
Genes
Hair
Cochlea
Auditory Hair Cells
Knockout Mice
Cell Cycle
Cell Transdifferentiation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Rocha-Sanchez, S. M., Scheetz, L. R., Contreras, M., Weston, M. D., Korte, M., McGee, J., & Walsh, E. J. (2011). Mature mice lacking Rbl2/p130 gene have supernumerary inner ear hair cells and supporting cells. Journal of Neuroscience, 31(24), 8883-8893. https://doi.org/10.1523/JNEUROSCI.5821-10.2011

Mature mice lacking Rbl2/p130 gene have supernumerary inner ear hair cells and supporting cells. / Rocha-Sanchez, Sonia M.; Scheetz, Laura R.; Contreras, Melissa; Weston, Michael D.; Korte, Megan; McGee, JoAnn; Walsh, Edward J.

In: Journal of Neuroscience, Vol. 31, No. 24, 15.06.2011, p. 8883-8893.

Research output: Contribution to journalArticle

Rocha-Sanchez, SM, Scheetz, LR, Contreras, M, Weston, MD, Korte, M, McGee, J & Walsh, EJ 2011, 'Mature mice lacking Rbl2/p130 gene have supernumerary inner ear hair cells and supporting cells', Journal of Neuroscience, vol. 31, no. 24, pp. 8883-8893. https://doi.org/10.1523/JNEUROSCI.5821-10.2011
Rocha-Sanchez SM, Scheetz LR, Contreras M, Weston MD, Korte M, McGee J et al. Mature mice lacking Rbl2/p130 gene have supernumerary inner ear hair cells and supporting cells. Journal of Neuroscience. 2011 Jun 15;31(24):8883-8893. https://doi.org/10.1523/JNEUROSCI.5821-10.2011
Rocha-Sanchez, Sonia M. ; Scheetz, Laura R. ; Contreras, Melissa ; Weston, Michael D. ; Korte, Megan ; McGee, JoAnn ; Walsh, Edward J. / Mature mice lacking Rbl2/p130 gene have supernumerary inner ear hair cells and supporting cells. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 24. pp. 8883-8893.
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