Lee Terrance, Shah Chirag, Xu Eugene Yujun
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Lurie 7-117, 303 E Superior Street, Chicago, IL 60611, USA.
Mol Hum Reprod. 2007 Nov;13(11):771-9. doi: 10.1093/molehr/gam069. Epub 2007 Sep 23.
We have entered a new era of genomics in biomedical research with the availability of genome-wide sequences and expression data, resulting in the identification of a huge number of novel reproductive genes. The challenge we are facing today is how to determine the function of those novel and known genes and their roles in normal reproductive physiology, such as gamete production, pregnancy and fertilization, and the disease physiology such as infertility, spontaneous abortion and gynecological cancers. Mouse genetics has contributed tremendously to our understanding of the genetic causes of human diseases in the past decades. The establishment of mouse mutations is an effective way to understand the function of many reproductive proteins. One of the fast-growing mouse mutagenesis technologies-gene trap mutagenesis-represents a cost-effective way to generate mutations because of the public availability of mouse embryonic stem (ES) cell lines carrying insertional mutations and the continuing expansion of those ES gene trap cell lines. We review here the gene trapping technology and in particular examine its efficacy in generating mouse mutations for reproductive research. Even with the existing gene trap cell lines, many of the genes important for reproductive function through traditional knockout and chemical mutagenesis have been trapped, demonstrating gene trapping's efficacy in mutating genes involved in reproductive development. Comparing genes expressed in specific reproductive sub-cellular organelles and in the entire testis and ovary with gene trap lines in the International Gene Trap Consortium (IGTC) database, we could identify a significant portion of those genes as having been trapped, representing a great resource for establishing mouse models for reproductive research. Establishment and analysis of these mouse models, for example, could help with identifying genetic abnormalities underlying male infertility and other reproductive diseases.
随着全基因组序列和表达数据的可得性，我们已经进入了生物医学研究的基因组学新时代，这使得大量新的生殖基因得以被识别。我们如今面临的挑战是如何确定这些新基因和已知基因的功能，以及它们在正常生殖生理过程（如配子产生、妊娠和受精）和疾病生理过程（如不孕、自然流产和妇科癌症）中的作用。在过去几十年里，小鼠遗传学极大地增进了我们对人类疾病遗传病因的理解。建立小鼠突变体是了解许多生殖蛋白功能的有效途径。快速发展的小鼠诱变技术之一——基因捕获诱变，因其携带插入突变的小鼠胚胎干细胞（ES）系的公开可得性以及这些ES基因捕获细胞系的不断扩充，成为一种经济高效的产生突变的方法。我们在此回顾基因捕获技术，尤其考察其在产生用于生殖研究的小鼠突变体方面的功效。即便有现有的基因捕获细胞系，许多通过传统基因敲除和化学诱变对生殖功能很重要的基因已被捕获，这证明了基因捕获在使参与生殖发育的基因发生突变方面的功效。将在特定生殖亚细胞器以及整个睾丸和卵巢中表达的基因与国际基因陷阱联盟（IGTC）数据库中的基因陷阱品系进行比较，我们能够识别出其中很大一部分基因已被捕获，这为建立生殖研究的小鼠模型提供了丰富资源。例如，建立和分析这些小鼠模型有助于识别男性不育和其他生殖疾病背后的遗传异常情况。
