Two ways to trap a gene in mice
- Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom
The sequencing of the human and mouse genomes has been heralded as one of the most important recent achievements in biological science. Attention has now turned to the functional annotation of the 25,000 or so genes encoded by the mammalian genome. Although there are many experimental approaches that address gene function, the most relevant approach for extrapolation to human development, physiology, and disease is to analyze the phenotype of mutations for each gene in a whole mammalian model, the mouse. Many phenotypes relevant to congenital traits and abnormal pathologies in humans have emerged from gene knockout studies in the mouse, providing a strong justification for expanding the collection of mouse mutants to include all genes. Recent discussions between funding agencies and the mouse genetics community (1, 2) have garnered support for an international, concerted effort to generate a resource of mutations in every gene in the mouse genome. This effort will use a combination of gene targeting and gene trapping in ES cells, two well established technologies that were developed in parallel in the late 1980s and gradually perfected over the years (3, 4). In this issue of PNAS, Friedel et al. (5) ingeniously combine gene targeting and gene trapping to mutate genes expressed in ES cells at a high efficiency. It may surprise many to learn that this hybrid method of “targeted trapping” is applicable to a majority of genes in the mouse.
Gene targeting has been widely used over the past 15 years to engineer precise modifications in the mouse genome. The collective efforts of many laboratories have thus far produced targeted mutations in ≈3,600 genes, or just <15% of the genome (a list of targeted gene mutations is maintained by The Jackson Laboratory, www.informatics.jax.org). Gene targeting relies on rare homologous recombination events between …
