Broad segmental progeroid changes in short-lived Ercc1(-/Δ7) mice

• Published in: Pathobiology of aging & age related diseases 2011, Vol.1
• Main Authors: Dollé, Martijn E T, Kuiper, Raoul V, Roodbergen, Marianne, Robinson, Joke, de Vlugt, Sisca, Wijnhoven, Susan W P, Beems, Rudolf B, de la Fonteyne, Liset, de With, Piet, van der Pluijm, Ingrid, Niedernhofer, Laura J, Hasty, Paul, Vijg, Jan, Hoeijmakers, Jan H J, van Steeg, Harry
• Format: Article
• Language: English
• ISSN: 2001-0001
• DOI: 10.3402/pba.v1i0.7219

Genome maintenance is considered a prime longevity assurance mechanism as apparent from many progeroid human syndromes that are caused by genome maintenance defects. The ERCC1 protein is involved in three genome maintenance systems: nucleotide excision repair, interstrand cross-link repair, and homologous recombination. Here we describe in-life and post-mortem observations for a hypomorphic Ercc1 variant, Ercc1(-/Δ7), which is hemizygous for a single truncated Ercc1 allele, encoding a protein lacking the last seven amino acids. Ercc1(-/Δ7) mice were much smaller and median life span was markedly reduced compared to wild-type siblings: 20 and 118 weeks, respectively. Multiple signs and symptoms of aging were found to occur at an accelerated rate in the Ercc1(-/Δ7) mice as compared to wild-type controls, including a decline in weight of both whole body and various organs, numerous histopathological lesions, and immune parameters. Together they define a segmental progeroid phenotype of the Ercc1(-/Δ7) mouse model.