Department of Neuroscience, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Mech Ageing Dev. 2013 May-Jun;134(5-6):180-95. doi: 10.1016/j.mad.2013.04.003. Epub 2013 Apr 13.
Cockayne syndrome (CS) is a rare multisystem disorder characterized by cachectic dwarfism, nervous system abnormalities and features of premature aging. CS symptoms are associated with mutations in 5 genes, CSA, CSB, XPB, XPD and XPG encoding for proteins involved in the transcription-coupled subpathway of nucleotide excision DNA repair (NER). Mutant mice have been generated for all CS-associated genes and provide tools to examine how the cellular defects translate into CS symptoms. Mice deficient for Csa or Csb genetically mimic CS in man, and develop mild CS symptoms including reduced fat tissue, photoreceptor cell loss, and mild, but characteristic, nervous system pathology. These mild CS models are converted into severe CS models with short life span, progressive nervous system degeneration and cachectic dwarfism after simultaneous complete inactivation of global genome NER. A spectrum of mild-to-severe CS-like symptoms occurs in Xpb, Xpd, and Xpg mice that genetically mimic patients with a disorder that combines CS symptoms with another NER syndrome, xeroderma pigmentosum. In conclusion, CS mouse models mice develop a range of CS phenotypes and open promising perspectives for testing interventional approaches.
科凯恩综合征（CS）是一种罕见的多系统疾病，其特征为恶病质侏儒、神经系统异常和早衰特征。CS 症状与 5 个基因的突变有关，CSA、CSB、XPB、XPD 和 XPG 编码参与核苷酸切除 DNA 修复（NER）转录偶联亚途径的蛋白质。所有与 CS 相关的基因都已生成突变小鼠，为研究细胞缺陷如何转化为 CS 症状提供了工具。缺乏 Csa 或 Csb 的基因敲除小鼠在体内模拟 CS，表现出轻度 CS 症状，包括脂肪组织减少、光感受器细胞丧失以及轻度但具有特征性的神经系统病变。这些轻度 CS 模型在全球基因组 NER 完全失活后，会转化为具有短寿命、进行性神经系统退化和恶病质侏儒的严重 CS 模型。Xpb、Xpd 和 Xpg 小鼠表现出一系列从轻度到重度的 CS 样症状，这些小鼠在体内模拟了另一种 NER 综合征——着色性干皮病与 CS 症状相结合的患者。总之，CS 小鼠模型发展出一系列 CS 表型，为测试干预方法提供了有希望的前景。
