Mutations in the CSB gene cause Cockayne syndrome (CS), a DNA repair disorder characterized by UV sensitivity and severe physical and neurological impairment. CSB functions in the transcription-coupled repair subpathway of nucleotide excision repair. This function may explain the UV sensitivity but hardly clarifies the other CS symptoms. Many of these, including retinopathy, are associated with premature aging. We studied eye pathology in a mouse model for CS. Csbm/mmice were hypersensitive to UV light and developed epithelial hyperplasia and squamous cell carcinomas in the cornea, which underscores the importance of transcription-coupled repair of photolesions in the mouse. In addition, we observed a spontaneous loss of retinal photoreceptor cells with age in the Csbm/mretina, resulting in a 60% decrease in the number of rods by the age of 18 months. Importantly, when Csbm/mmice (as well as Csa-/-mice) were exposed to 10 Gy of ionizing radiation, we noticed an increase in apoptotic photoreceptor cells, which was not observed in wild-type animals. This finding, together with our observation that the expression of established oxidative stress marker genes is upregulated in the Csbm/mretina, suggests that (endogenous) oxidative DNA lesions play a role in this CS-specific premature-aging feature and supports the oxidative DNA damage theory of aging. Copyright,
Molecular and Cellular Biology
Erasmus MC: University Medical Center Rotterdam

Gorgels, T., van der Pluijm, I., Brandt, R., Garinis, G., van Steeg, H., van den Aardweg, G., … van der Horst, G. (2007). Retinal degeneration and ionizing radiation hypersensitivity in a mouse model for cockayne syndrome. Molecular and Cellular Biology, 27(4), 1433–1441. doi:10.1128/MCB.01037-06