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

Authors :: Dollé ME
Kuiper RV
Roodbergen M
Robinson J
de Vlugt S
Wijnhoven SW
Beems RB
de la Fonteyne L
de With P
van der Pluijm I
Niedernhofer LJ
Hasty P
Vijg J
Hoeijmakers JH
van Steeg H
Source :: Pathobiology of aging & age related diseases [Pathobiol Aging Age Relat Dis] 2011; Vol. 1. Date of Electronic Publication: 2011 Jun 01.
Publication Year :: 2011
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.