This workpackage aims to establish a European virtual centre for targeted knock-out of genes of interest by resequencing of mutagenized fish (also known as TILLING). This technology, developed by Hubrecht Laboratory, allows to study the function of ‘difficult’ genes for which no mutations have been possible to recover by forward genetic screens, or which relate to processes that are difficult to study by forward genetic approaches, such as duplicated genes or functionally redundant genes. Our project is the first one to perform this type of work in a high-throughput manner.

The planned workload of 180 knock-outs is distributed between the laboratories of Sanger (D. Stemple), Hubrecht Laboratory (R. Plasterk and E. Cuppen) and TUD (M. Brand, previously at MPI CBG). This resource is open to all members of the consortium as well as external researchers. Up to 60 knock-outs will be performed for researchers outside the consortium, whose requests are considered on the basis of their scientific merit.

Submission of KO requests is now closed as we have received enough requests for the remainder of the ZF-MODELS project. However, additional KOs can be requested from the Zebrafish Mutation Resource (Sanger Institute) or from Sylke Winkler <winkler@mpi-cbg.de> (TUD).

The progress of previously submitted requests can be tracked through the internal knock-out website of Hubrecht Laboratory (login required).

Information on the knock-out mutants generated by the ZF-MODELS consortium is made publicly available through the public knock-out website of Hubrecht Laboratory, immediately after a knock-out is generated. Knock-out fish are immediately delivered to the requesters, with an MTA drawn up by the consortium.

Requesters are required by the MTA to offer the screening laboratory a co-authorship on any first publication describing the mutation. The requesters are responsible for keeping the knock-out fish lines delivered to them, and to submit them to a public stockcenter if they do not intend to keep them anylonger. Furthermore the requesters must redistribute their lines to external researchers on request, without further restrictions, starting 6 months after receipt.