Accelerated loss of hearing and vision in the DNA-repair deficient Ercc1 δ/- mouse

Marcella Spoor, A. Paul Nagtegaal, Yanto Ridwan, Nils Z. Borgesius, Bart van Alphen, Ingrid van der Pluijm, Jan H.J. Hoeijmakers, Maarten A. Frens, J. Gerard G. Borst

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

12 Citaten (Scopus)

Samenvatting

Age-related loss of hearing and vision are two very common disabling conditions, but the underlying mechanisms are still poorly understood. Damage by reactive oxygen species and other reactive cellular metabolites, which in turn may damage macromolecules such as DNA, has been implicated in both processes. To investigate whether DNA damage can contribute to age-related hearing and vision loss, we investigated hearing and vision in Ercc1 δ/- mutant mice, which are deficient in DNA repair of helix-distorting DNA lesions and interstrand DNA crosslinks. Ercc1 δ/- mice showed a progressive, accelerated increase of hearing level thresholds over time, most likely arising from deteriorating cochlear function. Ercc1 δ/- mutants also displayed a progressive decrease in contrast sensitivity followed by thinning of the outer nuclear layer of the eyeball. The strong parallels with normal ageing suggest that unrepaired DNA damage can induce age-related decline of the auditory and visual system.

Originele taal-2Engels
Pagina's (van-tot)59-67
Aantal pagina's9
TijdschriftMechanisms of Ageing and Development
Volume133
Nummer van het tijdschrift2-3
DOI's
StatusGepubliceerd - feb. 2012
Extern gepubliceerdJa

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