Inter Disciplinary Focus Meeting 'Mouse models for alternative splicing' report

The IFM on “Mouse models of alternative splicing” provided an overview of current state-of-the-art technologies for gene manipulation in mice as well as the application of these technologies to understand the in vivo function of splicing factors, alternatively spliced isoforms and their alterations in disease. The selection of speakers was a lucky one, not only because of the outstanding quality of their science, but also because their excellent presentations were adapted to a mostly non-specialized audience of splicing aficionados to illustrate the principles and possibilities opened by new advances in gene manipulation of animal models. Efficient recombination technologies are making possible to tackle high-throughput projects for gene knockout in ES cells. EURASNET members were somewhat disappointed to hear that there are no plans in such EU-funded massive knockout projects to extend these analyses to alternatively spliced exons. This realization should encourage both communities to lobby for large-scale analysis of spliced isoforms as a necessary step to describe gene regulation in higher eukaryotes in vivo. It also emerged that issues relevant to the correct processing of pre-mRNAs should be taken into consideration in the design of knock-out strategies. It is increasingly clear that tissue-specific knock-out and knock-in of splicing regulatory factors can not only provide essential tools to dissect splicing-related pathologies, but also that many completely unexpected insights on the physiological requirement and function of these factors and their regulation will be obtained. The long-term investment required to generate these reagents will be worthwhile, and a community effort to systematically generate animal models and analyze them at the molecular and phenotypic level would be a visionary step forward for our field.