Workpackage 1: Mutagenesis screening

Eye MutantsMutagenesis screens provide an unbiased and genome-wide, large-scale approach for identifying novel genes or gene functions. The MPI EB (C. Nüsslein-Volhard) is hosting a screen of 6,000 mutagenized genomes to isolate mutations specifically afflicting organogenesis and tissue formation, using technology established in previous large-scale screens. This screen uses the Tübingen line as a genetic background whose suitability has been proven in previous projects. Screening will also be performed for adult phenotypes displaying altered formation or growth of adult structures, as to date very little is known about the genetic basis underlying these processes, as well as impaired wound healing and behavioral abnormalities.

The Tübingen screen has been split in several phases. Each phase has a duration of 5 – 6 months and involves the screening of 1,500 – 2,500 families. This scheme allows for assays developed in the course of the project to be incorporated into later phases, resulting in more flexibility to maximize the scientific output of the workpackage.

In order to identify mutations with relevance for neurogenerative diseases in the dopaminergic system, like Parkinson's disease, a second screen of 1,000 mutagenized genomes will be carried out by U Freiburg in transgenic fish carrying green fluorescent protein (GFP) fusion proteins (generated in WP2). We anticipate a start of the screen in fall 2006.

How to participate

External scientists are invited to participate in the screens and to employ their own assays. Please apply to Dr. Brigitte Walderich or Prof. Wolfgang Driever for the Tübingen and Freiburg screen, respectively. As the number of screening slots is limited, there will be a review and selection of the assays proposed. Wherever possible, several proposed assays will be combined such that they can be carried out on the same batch of embryos.

Dissemination of results

Information on the phenotype of ENU mutants is made publicly available by the screening
laboratory which submits preliminary mutant descriptions to the public ZFIN database, 6
months after the initial identification, one batch of descriptions every 3 months. These
descriptions use the ZFIN-supplied PATO ontology along with a free-text description, and
will be updated after the re-screen if necessary.

As the ZF-MODELS consortium does not operate a stockcenter, the screen participants are
responsible for keeping the fish lines on which they plan to perform further work. The screen
participants must distribute their lines to external researchers on request, with a Material
Transfer Agreement (MTA) drawn up by the consortium, starting 24 months after release to
the database. However, they are free to distribute their lines earlier, with the same MTA.

External researchers are required by the MTA to offer a co-authorship on any first
publication describing the molecular identification of the mutation(s). Fish may be further
distributed by external researchers, without restrictions, starting 24 months after receipt or
after a first publication describing the molecular identification of the mutation(s), whatever
comes first.

Descriptions of the first 663 mutants were submitted to ZFIN in February 2006.