title: Broad segmental progeroid changes in short-lived Ercc1(-/Δ7) mice.
abstract: 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.
authors.affiliation: Laboratory of Heath Protection Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Martijn E T
authors.initials: ME
authors.lastname: Dollé
authors.forename: Raoul V
authors.initials: RV
authors.lastname: Kuiper
authors.forename: Marianne
authors.initials: M
authors.lastname: Roodbergen
authors.forename: Joke
authors.initials: J
authors.lastname: Robinson
authors.forename: Sisca
authors.initials: S
authors.lastname: de Vlugt
authors.forename: Susan W P
authors.initials: SW
authors.lastname: Wijnhoven
authors.forename: Rudolf B
authors.initials: RB
authors.lastname: Beems
authors.forename: Liset
authors.initials: L
authors.lastname: de la Fonteyne
authors.forename: Piet
authors.initials: P
authors.lastname: de With
authors.forename: Ingrid
authors.initials: I
authors.lastname: van der Pluijm
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Niedernhofer
authors.forename: Paul
authors.initials: P
authors.lastname: Hasty
authors.forename: Jan
authors.initials: J
authors.lastname: Vijg
authors.forename: Jan H J
authors.initials: JH
authors.lastname: Hoeijmakers
authors.forename: Harry
authors.initials: H
authors.lastname: van Steeg