Lack of &amp;lt;i&amp;gt;Rbl&amp;lt;/i&amp;gt;1/p107 Effects on Cell Proliferation and Maturation in the Inner Ear

Rocha-Sánchez, Sonia M.; Scheetz, Laura R.; Siddiqi, Sabrina; Weston, Michael W.; Smith, Lynette M.; Dempsey, K. P.; Ali, Hesham H.; McGee, JoAnn; Walsh, Edward J.

doi:10.4236/jbbs.2013.37056

Cited by 3 publications

(2 citation statements)

References 53 publications

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“…More GO terms were enriched by putative genes associated with otitis media, including non−membrane spanning protein tyrosine kinase activity (GO:0004715) and interleukin mediated signaling pathway (GO:0038100, GO0035723). Non-membrane spanning protein tyrosine kinase has been shown to be associated with specific inflammatory effects and pathogen infections ( Gu et al, 2009 ; Rocha-Sanchez et al, 2013 ). Considering that otitis media is associated with infection and inflammatory effects around middle ears, it is reasonable for otitis media associated genes to enrich in inflammatory effects.…”

Section: Discussionmentioning

confidence: 99%

Use of a Network-Based Method to Identify Latent Genes Associated with Hearing Loss in Children

Liang

Ding

et al. 2021

Front. Cell Dev. Biol.

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Hearing loss is a total or partial inability to hear. Approximately 5% of people worldwide experience this condition. Hearing capacity is closely related to language, social, and basic emotional development; hearing loss is particularly serious in children. The pathogenesis of childhood hearing loss remains poorly understood. Here, we sought to identify new genes potentially associated with two types of hearing loss in children: congenital deafness and otitis media. We used a network-based method incorporating a random walk with restart algorithm, as well as a protein-protein interaction framework, to identify genes potentially associated with either pathogenesis. A following screening procedure was performed and 18 and 87 genes were identified, which potentially involved in the development of congenital deafness or otitis media, respectively. These findings provide novel biomarkers for clinical screening of childhood deafness; they contribute to a genetic understanding of the pathogenetic mechanisms involved.

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Section: Discussionmentioning

confidence: 99%

Use of a Network-Based Method to Identify Latent Genes Associated with Hearing Loss in Children

Liang

Ding

et al. 2021

Front. Cell Dev. Biol.

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“…In addition to its well-established importance in development and cancer research, special attention has been paid to the role of Rb1 in tissue regeneration ( Bakay et al, 2006 ; Wang et al, 2013 ), particularly auditory HC regeneration ( Mantela et al, 2005 ; Sage et al, 2005 , 2006 ; Weber et al, 2008 ). During the past 8 years, using the auditory system as a model, we and others have shown that manipulation of the Rb1 gene or specific components of the Rb1 pathway trigger unscheduled proliferation of the otherwise mitotically quiescent neurosensory HCs and their clonally related supporting cells ( Mantela et al, 2005 ; Sage et al, 2005 ; Weber et al, 2008 ; Rocha-Sanchez et al, 2011 , 2013 ). Although a growing repertoire of molecular techniques has substantially contributed to our understanding of the multifaceted role of Rb1 , no approach to date has been effective in allowing for the understanding of RB1 activity without permanently eliminating its activity, which, given Rb1 ’s broad spectrum of interactions, generally results in either impaired viability or morbidity ( Lee et al, 1992 ; Wu et al, 2003 ).…”

Section: Discussionmentioning

confidence: 99%

Generation of a Retinoblastoma (Rb)1-inducible dominant-negative (DN) mouse model

Tarang

Doi

Gurumurthy

et al. 2015

Front. Cell. Neurosci.

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Retinoblastoma 1 (Rb1) is an essential gene regulating cellular proliferation, differentiation, and homeostasis. To exert these functions, Rb1 is recruited and physically interacts with a growing variety of signaling pathways. While Rb1 does not appear to be ubiquitously expressed, its expression has been confirmed in a variety of hematopoietic and neuronal-derived cells, including the inner ear hair cells (HCs). Studies in transgenic mice demonstrate that complete germline or conditional Rb1 deletion leads to abnormal cell proliferation, followed by massive apoptosis; making it difficult to fully address Rb1’s biochemical activities. To overcome these limitations, we developed a tetracycline-inducible TetO-CB-myc6-Rb1 (CBRb) mouse model to achieve transient and inducible dominant-negative (DN) inhibition of the endogenous RB1 protein. Our strategy involved fusing the Rb1 gene to the lysosomal protease pre-procathepsin B (CB), thus allowing for further routing of the DN-CBRb fusion protein and its interacting complexes for proteolytic degradation. Moreover, reversibility of the system is achieved upon suppression of doxycycline (Dox) administration. Preliminary characterization of DN-CBRb mice bred to a ubiquitous rtTA mouse line demonstrated a significant inhibition of the endogenous RB1 protein in the inner ear and in a number of other organs where RB1 is expressed. Examination of the postnatal (P) DN-CBRb mice inner ear at P10 and P28 showed the presence of supernumerary inner HCs (IHCs) in the lower turns of the cochleae, which corresponds to the described expression domain of the endogenous Rb1 gene. Selective and reversible suppression of gene expression is both an experimental tool for defining function and a potential means to medical therapy. Given the limitations associated with Rb1-null mice lethality, this model provides a valuable resource for understanding RB1 activity, relative contribution to HC regeneration and its potential therapeutic application.

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Spatiotemporally controlled overexpression of cyclin D1 triggers generation of supernumerary cells in the postnatal mouse inner ear

et al. 2020

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Lack of <i>Rbl</i>1/p107 Effects on Cell Proliferation and Maturation in the Inner Ear

Cited by 3 publications

References 53 publications

Use of a Network-Based Method to Identify Latent Genes Associated with Hearing Loss in Children

Use of a Network-Based Method to Identify Latent Genes Associated with Hearing Loss in Children

Generation of a Retinoblastoma (Rb)1-inducible dominant-negative (DN) mouse model

Spatiotemporally controlled overexpression of cyclin D1 triggers generation of supernumerary cells in the postnatal mouse inner ear

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