Skeletal dysplasias, growth retardation, reduced postnatal survival, and impaired fertility in mice lacking the SNF2/SWI2 family member ETL1.
Skeletal dysplasias, growth retardation, reduced postnatal survival, and impaired fertility in mice lacking the SNF2/SWI2 family member ETL1.
复制标题
缺乏 SNF2/SWI2 家族成员 ETL1 的小鼠出现骨骼发育不良、生长迟缓、产后存活率降低和生育能力受损。
DOI：
10.1016/s0925-4773(99)00090-8
复制
发表时间：
1999
影响因子：
2.6
通讯作者：
Gossler,A
中科院分区：
文献类型：
--
作者：
Schoor,M;Schuster-Gossler,K;Roopenian,D;Gossler,A
小鼠Etl 1基因编码属于快速生长的SNF 2/SWI 2家族的核蛋白。该家族的成员与解旋酶和核酸依赖性ATP酶相关，并且在基本细胞过程中具有功能，例如转录调节、染色体稳定性的维持和DNA修复的各个方面。ETL 1蛋白从两细胞阶段开始表达，在整个胚胎发生过程中以动态模式表达，在胸腺、上皮和神经系统以及大多数成体组织中表达水平特别高。作为解决ETL 1在细胞和发育过程中的作用的第一步，我们通过同源重组使该基因失活。ES细胞和缺乏可检测到的ETL 1蛋白的小鼠是存活的，表明ETL 1对于细胞存活或胚胎发育不是必需的。然而，突变小鼠表现出生长迟缓，出生后/纳塔尔后死亡，生育能力降低和胸骨和脊柱的各种缺陷。所有观察到的表型的表达度和表达率都受到遗传背景的影响。缺乏ETL 1的同基因129 SvPasmice具有严重减少的胸腔容积，这可能导致呼吸衰竭，并且可以解释在这种遗传背景下围产期死亡的高发生率。
The mouse Etl1 gene encodes a nuclear protein belonging to the rapidly growing SNF2/SWI2 family. Members of this family are related to helicases and nucleic-acid-dependent ATPases and have functions in essential cellular processes such as transcriptional regulation, maintenance of chromosome stability and various aspects of DNA repair. The ETL1 protein is expressed from the two-cell stage onwards, throughout embryogenesis in a dynamic pattern with particularly high levels in the thymus, epithelia and the nervous system and in most adult tissues. As a first step to address the role of ETL1 in cells and during development, we inactivated the gene by homologous recombination. ES cells and mice lacking detectable ETL1 protein were viable, indicating that ETL1 is not essential for cell survival or for embryonic development. However, mutant mice showed retarded growth, peri/post natal lethality, reduced fertility and various defects in the sternum and vertebral column. Expressivity and penetrance of all observed phenotypes were influenced by the genetic background. Isogenic 129SvPasmice lacking ETL1 had a severely reduced thoracic volume, which might lead to respiratory failure and could account for the high incidence of perinatal death on this genetic background.