Nolan P M, Peters J, Strivens M, Rogers D, Hagan J, Spurr N, Gray I C, Vizor L, Brooker D, Whitehill E, Washbourne R, Hough T, Greenaway S, Hewitt M, Liu X, McCormack S, Pickford K, Selley R, Wells C, Tymowska-Lalanne Z, Roby P, Glenister P, Thornton C, Thaung C, Stevenson J A, Arkell R, Mburu P, Hardisty R, Kiernan A, Erven A, Steel K P, Voegeling S, Guenet J L, Nickols C, Sadri R, Nasse M, Isaacs A, Davies K, Browne M, Fisher E M, Martin J, Rastan S, Brown S D, Hunter J
MRC Mammalian Genetics Unit and Mouse Genome Centre, Harwell, UK.
Nat Genet. 2000 Aug;25(4):440-3. doi: 10.1038/78140.
As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics.
随着人类基因组计划接近尾声，哺乳动物遗传学家面临的挑战是开发系统确定哺乳动物基因功能的方法。小鼠诱变将是基因功能研究的关键要素。使用化学诱变剂N-乙基-N-亚硝基脲（ENU）的表型驱动方法是产生大量可筛选新表型的突变小鼠的潜在有效途径。这种方法的优点是，在评估基因功能时，无需对任何途径中涉及的基因做先验假设。因此，表型驱动诱变是鉴定新基因和新途径的有效方法。我们对小鼠进行了全基因组范围的表型驱动显性突变筛选。我们培育并筛选了超过26,000只小鼠，获得了约500个新的小鼠突变体。我们的工作以及随附论文中报道的项目，极大地增加了小鼠突变体资源，代表了哺乳动物遗传学中基因功能系统研究的第一步。
