A genetic approach to understanding gene function in mammals on large scale will be undertaken. This genetic analysis will complement current efforts to understand the human genome. By mutating genes in the mouse, gene function can be studied directly and the knowledge gained can be applied to human biology. In the case of human genetic disorders, the mouse mutation offers a potentially invaluable model to assess treatments and potential cures. The immediate goal of the project described here is to generate a large library of random mouse mutations-eventually representing every gene in the mouse genome. These mutations will be caused by insertion of a retroviral 'gene trapping' vector into the genome of embryonic stem (ES) cells. Large numbers of individually mutated clones will be isolated and stored. Sequence information from each disrupted gene will be obtained and used to build a database. From this resource, it is a simple matter to choose a gene based on sequence information., thaw the corresponding ES cell clone, and generate a mutant mouse line. Alternatively, mutations which cause a specific phenotype can be used to identify new genes whose function is important in some defined physiological or developmental circumstance.Proposed commercial application:The goal of this project is a library of ES cell clones, each with a unique insertion mutation. In this library, every gene in the mouse genome will be represented. In addition, each clone will be cross-referenced to a expressed sequence tag of approximately 300 bases. This resource is of commercial value since any gene or gene family of interest to an investigator in academia or industry can be identified in our library, the ES cell line thawed and a mouse line mutant for that gene generated immediately.National institute of Human Development (NIHD)
