title: Cockayne syndrome pathogenesis: lessons from mouse models.
abstract: Cockayne syndrome (CS) is a rare multisystem disorder characterized by cachectic dwarfism, nervous system abnormalities and features of premature aging. CS symptoms are associated with mutations in 5 genes, CSA, CSB, XPB, XPD and XPG encoding for proteins involved in the transcription-coupled subpathway of nucleotide excision DNA repair (NER). Mutant mice have been generated for all CS-associated genes and provide tools to examine how the cellular defects translate into CS symptoms. Mice deficient for Csa or Csb genetically mimic CS in man, and develop mild CS symptoms including reduced fat tissue, photoreceptor cell loss, and mild, but characteristic, nervous system pathology. These mild CS models are converted into severe CS models with short life span, progressive nervous system degeneration and cachectic dwarfism after simultaneous complete inactivation of global genome NER. A spectrum of mild-to-severe CS-like symptoms occurs in Xpb, Xpd, and Xpg mice that genetically mimic patients with a disorder that combines CS symptoms with another NER syndrome, xeroderma pigmentosum. In conclusion, CS mouse models mice develop a range of CS phenotypes and open promising perspectives for testing interventional approaches.
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. d.jaarsma@erasmusmc.nl
authors.forename: Dick
authors.initials: D
authors.lastname: Jaarsma
authors.forename: Ingrid
authors.initials: I
authors.lastname: van der Pluijm
authors.forename: Gijsbertus T J
authors.initials: GT
authors.lastname: van der Horst
authors.forename: Jan H J
authors.initials: JH
authors.lastname: Hoeijmakers
mesh_terms: D000818:Animals; D003057:Cockayne Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004260:DNA Repair; D004195:Disease Models, Animal; D006801:Humans; D008136:Longevity / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D014157:Transcription Factors