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
Laboratory of Heath Protection Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
Pathobiol Aging Age Relat Dis. 2011;1. doi: 10.3402/pba.v1i0.7219. Epub 2011 Jun 1.
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.
基因组维持被认为是一种主要的长寿保障机制，这在许多由基因组维持缺陷引起的早衰型人类综合征中显而易见。ERCC1蛋白参与三种基因组维持系统：核苷酸切除修复、链间交联修复和同源重组。在这里，我们描述了一种低表达的Ercc1变体Ercc1(-/Δ7)的生前和死后观察结果，该变体对于单个截短的Ercc1等位基因是半合子，编码一种缺少最后七个氨基酸的蛋白质。与野生型同胞相比，Ercc1(-/Δ7)小鼠体型小得多，中位寿命显著缩短：分别为20周和118周。与野生型对照相比，发现Ercc1(-/Δ7)小鼠衰老的多种体征和症状加速出现，包括全身和各种器官重量下降、众多组织病理学病变以及免疫参数。这些共同定义了Ercc1(-/Δ7)小鼠模型的部分早衰表型。
