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

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
Source :: Pathobiology of Aging & Age-related Diseases. 2011, Vol. 1, Special section p1-N.PAG. 14p.
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 mice-/Δ7 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. [ABSTRACT FROM AUTHOR]