Kile Benjamin T, Hentges Kathryn E, Clark Amander T, Nakamura Hisashi, Salinger Andrew P, Liu Bin, Box Neil, Stockton David W, Johnson Randy L, Behringer Richard R, Bradley Allan, Justice Monica J
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Nature. 2003 Sep 4;425(6953):81-6. doi: 10.1038/nature01865.
Now that the mouse and human genome sequences are complete, biologists need systematic approaches to determine the function of each gene. A powerful way to discover gene function is to determine the consequence of mutations in living organisms. Large-scale production of mouse mutations with the point mutagen N-ethyl-N-nitrosourea (ENU) is a key strategy for analysing the human genome because mouse mutants will reveal functions unique to mammals, and many may model human diseases. To examine genes conserved between human and mouse, we performed a recessive ENU mutagenesis screen that uses a balancer chromosome, inversion chromosome 11 (refs 4, 5). Initially identified in the fruitfly, balancer chromosomes are valuable genetic tools that allow the easy isolation of mutations on selected chromosomes. Here we show the isolation of 230 new recessive mouse mutations, 88 of which are on chromosome 11. This genetic strategy efficiently generates and maps mutations on a single chromosome, even as mutations throughout the genome are discovered. The mutations reveal new defects in haematopoiesis, craniofacial and cardiovascular development, and fertility.
既然小鼠和人类基因组序列已经完成，生物学家需要系统的方法来确定每个基因的功能。发现基因功能的一个有效方法是确定活生物体中突变的后果。用点突变剂N-乙基-N-亚硝基脲（ENU）大规模产生小鼠突变是分析人类基因组的关键策略，因为小鼠突变体将揭示哺乳动物特有的功能，而且许多可能成为人类疾病的模型。为了研究人类和小鼠之间保守的基因，我们进行了一次隐性ENU诱变筛选，该筛选使用了一条平衡染色体，即11号倒位染色体（参考文献4、5）。平衡染色体最初是在果蝇中发现的，是有价值的遗传工具，可使在选定染色体上的突变易于分离。在这里，我们展示了230个新的隐性小鼠突变的分离，其中88个位于11号染色体上。这种遗传策略即使在发现全基因组突变的情况下，也能有效地在单条染色体上产生并定位突变。这些突变揭示了造血、颅面和心血管发育以及生育能力方面的新缺陷。
