Munich

Mouse geneticists in Europe have launched an initiative to standardize the flood of data being generated by studies of mouse mutants.

At a meeting in Paris last week, the heads of European mouse-genetics research centres agreed to unify the screening processes used to identify mouse mutants that may aid studies of human diseases.

Steve Brown wants a two-pronged test for mutant mice. Credit: MRC HARWELL

The 17 members of EUMORPHIA — the European Union Mouse Research for Public Health and Industrial Applications network — plan to use two levels of screens, and to make full descriptions of the mutants available on a public database.

“The first level would hopefully be applied to all mutants,” explains Steve Brown, director of the Medical Research Council's Mammalian Genetics Unit at Harwell, UK, and one of the two researchers running EUMORPHIA. “We'll design a fast series of tests to answer simple questions. Are the mice deaf? Are they overweight?” Second-level tests will then be used to take a more thorough look at the unusual characteristics identified in the first screen.

In the past four years, hundreds of mouse mutants have been created by random chemical mutagenesis, in which chemicals are used to introduce a random mutation into the animal's genome. Researchers study the effect of the mutation and, if the resulting characteristics are interesting, identify the gene responsible.

Knockout mice, in which a specific gene is targeted and disabled, are also widely used to model and study human diseases. The rate at which both types of mutant are being created has been accelerating as the mouse genome sequence nears completion.

Two centres — the GSF national research centre in Munich and the Harwell unit — have been screening mutants generated by chemical mutagenesis, and have already identified nearly 600 types that may be useful in disease studies.

Screen star: standardized tests for mutant mice may speed up research into human diseases. Credit: MRC HARWELL

Some of the standardized tests will be based on those already used at Munich and Harwell, with the task of defining the others being split between EUMORPHIA members. Experts from outside Europe will also be invited to participate, and EUMORPHIA members hope that the tests will soon be adopted globally.

Knockout mice could also be screened using the new tests, says Pierre Chambon, director of the Institute of Genetics and Molecular and Cellular Biology in Strasbourg, France, and the other EUMORPHIA leader.

This could be beneficial, he adds, recalling an incident when he discovered by chance a link between retinoic acid and the neurotransmitter dopamine. While studying developmental problems, one of the knockout mutants he produced showed some symptoms reminiscent of Parkinson's disease — in which the brain's dopamine system is defective. “It turned out that one of the brain's dopamine receptors is regulated by an element controlled by retinoic acid,” says Chambon. He hopes that such chance findings will become routine if knockouts are screened.