Impaired genome maintenance suppresses the growth hormone-insulin-like growth factor 1 axis in mice with cockayne syndrome

Ingrid Van Der Pluijm, George A. Garinis, Renata M.C. Brandt, Theo G.M.F. Gorgels, Susan W. Wijnhoven, Karin E.M. Diderich, Jan De Wit, James R. Mitchell, Conny Van Oostrom, Rudolf Beems, Laura J. Niedernhofer, Susana Velasco, Errol C. Friedberg, Kiyoji Tanaka, Harry Van Steeg, Jan H.J. Hoeijmakers, Gijsbertus T.J. Van Der Horst

Research output: Contribution to journalArticlepeer-review

197 Scopus citations


Cockayne syndrome (CS) is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER). Here, complete inactivation of NER in Csbm/m/Xpa-/- mutants causes a phenotype that reliably mimics the human progeroid CS syndrome. Newborn Csbm/m/ Xpa-/- mice display attenuated growth, progressive neurological dysfunction, retinal degeneration, cachexia, kyphosis, and die before weaning. Mouse liver transcriptome analysis and several physiological endpoints revealed systemic suppression of the growth hormone/insulin-like growth factor 1 (GH/IGF1) somatotroph axis and oxidative metabolism, increased antioxidant responses, and hypoglycemia together with hepatic glycogen and fat accumulation. Broad genome-wide parallels between Csbm/m/Xpa-/- and naturally aged mouse liver transcriptomes suggested that these changes are intrinsic to natural ageing and the DNA repair-deficient mice. Importantly, wild-type mice exposed to a low dose of chronic genotoxic stress recapitulated this response, thereby pointing to a novel link between genome instability and the age-related decline of the somatotroph axis.

Original languageEnglish (US)
Pages (from-to)23-38
Number of pages16
JournalPLoS biology
Issue number1
StatePublished - Jan 2007

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)


Dive into the research topics of 'Impaired genome maintenance suppresses the growth hormone-insulin-like growth factor 1 axis in mice with cockayne syndrome'. Together they form a unique fingerprint.

Cite this