Broad segmental progeroid changes in short- lived Ercc1-/Δ7 mice
Broad segmental progeroid changes in short- lived Ercc1-/Δ7 mice
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DOI：
10.3402/pba.v1i0.7219
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发表时间：
2011-01-01
期刊：
影响因子：
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通讯作者：
van Steeg, Harry
中科院分区：
文献类型：
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作者：
Dolle, Martijn E. T.;Kuiper, Raoul V.;van Steeg, Harry
基因组维持被认为是主要的长寿保证机制，从许多由基因组维持缺陷引起的类早衰人类综合征中可以明显看出。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，我们描述了对Ercc1的半胚变异Ercc1（-/Delta 7）的生前和死后观察，它是一个截断的Ercc1等位基因的半合子，编码缺乏最后7个氨基酸的蛋白质。与野生型兄弟姐妹相比，Ercc1（-/Delta 7）小鼠体积小得多，平均寿命明显缩短：分别为20周和118周。研究发现，与野生型对照相比，Ercc1（-/Delta 7）小鼠的多种衰老体征和症状以更快的速度发生，包括全身和各器官的体重下降、许多组织病理学病变和免疫参数。它们共同定义了Ercc1（-/Delta 7）小鼠模型的节段性类早衰表型。
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(-/Delta 7), which is hemizygous for a single truncated Ercc1 allele, encoding a protein lacking the last seven amino acids. Ercc1(-/Delta 7) 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(-/Delta 7) 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(-/Delta 7) mouse model.