Cockayne syndrome group B (Csb) and group a (Csa) deficiencies predispose to hearing loss and cochlear hair cell degeneration in mice

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
A Paul NagtegaalNeil Segil

Abstract

Sensory hair cells in the cochlea, like most neuronal populations that are postmitotic, terminally differentiated, and non-regenerating, depend on robust mechanisms of self-renewal for lifelong survival. We report that hair cell homeostasis requires a specific sub-branch of the DNA damage nucleotide excision repair pathway, termed transcription-coupled repair (TCR). Cockayne syndrome (CS), caused by defects in TCR, is a rare DNA repair disorder with a broad clinical spectrum that includes sensorineural hearing loss. We tested hearing and analyzed the cellular integrity of the organ of Corti in two mouse models of this disease with mutations in the Csb gene (CSB(m/m) mice) and Csa gene (Csa(-/-) mice), respectively. Csb(m/m) and Csa(-/-) mice manifested progressive hearing loss, as measured by an increase in auditory brainstem response thresholds. In contrast to wild-type mice, mutant mice showed reduced or absent otoacoustic emissions, suggesting cochlear outer hair cell impairment. Hearing loss in Csb(m/m) and Csa(-/-) mice correlated with progressive hair cell loss in the base of the organ of Corti, starting between 6 and 13 weeks of age, which increased by 16 weeks of age in a basal-to-apical gradient, with outer hair cells ...Continue Reading

Citations

Oct 22, 2016·Ageing Research Reviews·Ajoy C KarikkinethVilhelm A Bohr
Apr 13, 2018·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Ophir Handzel, Joseph B Nadol
May 27, 2020·Genetics and Molecular Biology·Alexandre Teixeira VessoniCamila Carrião Machado Garcia
Jan 15, 2020·Npj Aging and Mechanisms of Disease·Mustafa N OkurVilhelm A Bohr
Oct 7, 2020·Nucleic Acids Research·Amanda F C LopesBjörn Schumacher
Jan 7, 2021·Npj Aging and Mechanisms of Disease·Mustafa N OkurVilhelm A Bohr
Sep 8, 2019·Hearing Research·Krishna BommakantiKonstantina M Stankovic
May 13, 2018·Trends in Molecular Medicine·Douglas E BrashUNKNOWN Excited-State Medicine Working Group
Jun 7, 2018·Cell Metabolism·Mark P Mattson, Thiruma V Arumugam

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