Yates Laura, McMurray Fiona, Zhang Youming, Greenfield Andy, Moffatt Miriam, Cookson William, Dean Charlotte
MRC Harwell, Harwell, Oxfordshire OX11 0RD, UK.
Biochem Soc Trans. 2009 Aug;37(Pt 4):838-42. doi: 10.1042/BST0370838.
ENU (N-ethyl-N-nitrosourea) is a chemical mutagen that randomly induces point mutations in DNA. Since the 1990s ENU has been successfully used as a means to obtain mouse mutants using both gene-driven (reverse genetics) and phenotype-driven (forward genetics) approaches. A high-efficiency ENU approach results in approx. 25 functional mutations per genome; most of these will result in hypomorphic alleles. Our group has recently begun using ENU mutagenesis as a tool for understanding lung development and disease. In collaboration with other groups at MRC Harwell, we have undertaken a screen for recessive mutations affecting mouse lung development. We are currently pursuing two lines identified from this screen, Hel (head, eye and lung) and RecBA17. Both these lines exhibit lung defects and we believe that by studying the phenotypes and identifying the causative mutations, we may also shed light on lung disease pathogenesis. In collaboration with Bill Cookson and Miriam Moffatt, we are also taking a gene-driven approach for understanding asthma. Using the Harwell ENU sperm archive, we have recovered mouse lines harbouring mutations in the asthma-susceptibility genes Phf11 (PHD finger protein 11) and Dpp10 (dipeptidylpeptidase 10). Functional analyses of these alleles are currently under way.
ENU（N-乙基-N-亚硝基脲）是一种化学诱变剂，可随机诱导DNA发生点突变。自20世纪90年代以来，ENU已成功用作通过基因驱动（反向遗传学）和表型驱动（正向遗传学）方法获得小鼠突变体的手段。高效ENU方法可在每个基因组中产生约25个功能性突变；其中大多数将导致亚效等位基因。我们小组最近开始使用ENU诱变作为理解肺发育和疾病的工具。与MRC哈韦尔的其他小组合作，我们对影响小鼠肺发育的隐性突变进行了筛选。我们目前正在研究从该筛选中鉴定出的两个品系，Hel（头、眼和肺）和RecBA17。这两个品系均表现出肺部缺陷，我们相信通过研究这些表型并鉴定致病突变，我们或许还能阐明肺部疾病的发病机制。与比尔·库克森和米里亚姆·莫法特合作，我们也在采用基因驱动方法来理解哮喘。利用哈韦尔ENU精子库，我们获得了在哮喘易感基因Phf11（PHD指蛋白11）和Dpp10（二肽基肽酶10）中携带突变的小鼠品系。目前正在对这些等位基因进行功能分析。
