Gene trap mutagenesis: a functional genomics approach towards reproductive research

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.