We will generate knock-out mutations in at least 1,000 regulatory genes relevant for common human diseases, and maintain and distribute the mutant stocks as well as information on the mutations to researchers inside and outside the Consortium.
Specifically, we will use the TILLING method to knock out at least 1,000 regulatory genes (transcription factors) in the zebrafish. Priority will be given to genes within critical regions of mapped human disease loci. This effort (coordinated by GRL, UK, with support from KNAW, Netherlands, and TUD, Germany) is made possible by high-throughput TILLING protocols and software developed in the FP6 ZF-MODELS project.
We will also establish a pipeline for the newly developed Zinc Finger Nuclease method (by KIT-G, MPG and UCO, Germany, and USFD, UK), which we will use to mutate a minimum of 30 (but possibly up to 300) additional regulatory genes. This approach is not yet established as a high- throughput method and will require considerable technology development. It will however be of great value as complement to the TILLING resource, primarily for genes where TILLING is problematic, e.g. because of a short coding sequence, because of repeats, or where specific mutations are required.
(Work Package Leader: GRL)