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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

201 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)23-38
Aantal pagina's16
TijdschriftPLoS Biology
Nummer van het tijdschrift1
StatusGepubliceerd - jan. 2007
Extern gepubliceerdJa


Duik in de onderzoeksthema's van 'Impaired genome maintenance suppresses the growth hormone-insulin-like growth factor 1 axis in mice with cockayne syndrome'. Samen vormen ze een unieke vingerafdruk.

Citeer dit