Cockayne syndrome (CS) is a congenital syndrome characterized by growth and development, mental retardation, and premature aging. It is an autosomal recessive genetic disease that occurs in 2.5 cases per million births worldwide and caused by mutations in two genes ERCC8 (also known as CSA) and ERCC6 (commonly known as CSB), which account for CS 20% and 80% of cases, respectively. Due to the complexity of CS and mammalian models, simpler metazoan models are needed to display CS-like phenotypes, which can be studied in the context of living organisms.
C.elegans is widely used as a simple model organism to uncover complex mechanisms involving in the DNA damage response and human diseases, particularly in the context of ageing. Björn Schumacher and his research team establish phenotypic parallels between human CS and C. elegans carrying a csb-1 mutation that allows investigating the underlying role of DNA damage in accelerating neuronal degeneration in vivo. The csb-1(lf) C.elegans adult is enhanced UV-induced DNA damage which degrades when DNA is damaged and exhibited dysfunctional hyperfusion mitochondria, leading to reduced respiratory activity.
The findings in the article support the role of endogenous DNA damage as a driving factor in CS-related neuropathology, and emphasize the role of mitochondrial dysfunction in the disease. C. elegans CS model might thus yield important new insight into the causal role of DNA damage in the age-related progressive loss of neuronal integrity and provide an experimental model for neurodegenerative diseases.
Lopes AFC, Bozek K, Herholz M, Trifunovic A, Rieckher M, Schumacher B. A C. elegans model for neurodegeneration in Cockayne syndrome. (2020) Nucleic Acids Res. doi: 10.1093/nar/gkaa795