These GM mice also can be used to show how human disorders appear and, more importantly, how they may be treated and cured.

Some figures may give an idea of the exploding needs of these mice for research:

· In terms of specimen, in the UK alone, some 500,000 mutant mice were used in 1999, as recently reported by the British Royal Society. France plans to handle some 60 to 70 thousand specimens of mutant mice in a new facility to be built at the Génopole in Strasbourg over the coming years.

· In terms of new types of mutants, over the last ten years, 2,500 mutant lines have been identified. Recently, two groups led by laboratories involved in the European Mutant Mouse Archive consortium (EMMA) reported last year in Nature Genetics that they have created 500 and 429 new mutants respectively in the framework of National Genome projects.

The interest of keeping this increasing number of genetically modified mice is enormous, as creating, screening and characterizing those mutants requires a heavy investment.

Moreover, the development of new techniques to generate mutants opens the way to a systematic creation of new strains that can then be stored for subsequent use in biomedical research.

The expected result is to have an efficient archive of mutant mice offering the scientific community efficient search mechanisms a well as access and delivery methods of the desired strains. This is what the EMMA consortium is committed to achieve, using European Community funds that will be made available upon successful conclusion of ongoing negotiations.

Why the mouse?

Mice are small, they grow fast and reproduce quickly. And because they are mammals, they share with humans most of its genome, which turns out to be of similar size and to have a comparable number of genes. This makes mice a suitable model for human genomics and human health research.

For the last 20 years, the mouse has been used to reproduce on a smaller scale the conditions leading to disorders of major concern for humans, particularly cancer. The mouse also provides a controlled environment to test the effectiveness of new drugs that later on will be developed into medicines for humans.

With the advent of genomics knowledge, the mouse becomes increasingly interesting for geneticists and doctors as they develop the ability to tailor the genetic constitution of the offspring, therefore allowing them to create strains with the desired genotype and phenotype characteristics.

New technologies have been developed that allow scientists to rapidly generate new types of mutants, be it by eliminating genes (knock-out), by transferring new ones, or even by introducing genes from other species, for example, human.

Usually, all these changes are induced at the early stages of development in the embryos. Most recently, new techniques allow producing changes in adults at a specific age and in target tissues.

Studies based on mutant mice have produced spectacular advances in human health research. Some examples: in understanding the origin and etiology of breast cancer, in repairing heart tissue destroyed after an infarct, or in unraveling unknown pigments in eyes that may be responsible for the circadian rhythms in mammals.

Storing and maintaining strains of mutant mice is a complicated business. Stock centers require strict application of sanitary and security rules to avoid internal and external contamination.

Highly specialized and trained personnel is needed at every level of the management chain of the stock center, to a point that even the cleaning of cages and feeding of animals require extreme care and technical, non-obvious knowledge.

Only a fraction of the mutants are stored as living animals. An important stock potential of the facility is the capacity to maintain frozen embryos and sperm from which complete individuals may be restored when needed. Also, the living stocks require regular renewal to ensure an acceptable level of availability of specimens.

Every mutant line needs to store 500 frozen embryos, and needs to be replaced when stock falls under 250 embryos; it needs 30 aliquots of frozen sperm to be kept; and finally, the live stock of highly demanded lines requires some 50 animals permanently available.

Taking into consideration all overhead costs, personnel, training and databasing, the average cost of storing and maintaining each mutant line is between EUR 5,000 and 7,000.

The European Mutant Mouse Archive is not one center, but a network of stock centers and research institutions involved in biomedical research. Currently, seven groups constitute the network, but new ones will join in the new future.

The network aims at working as a single entity that will be virtually perceived by users as a single center. Yet the seven partners contribute to the project with their own animal facilities, personnel and equipment.

Key to the success of this perception as one single facility is the development of the EMMA Resource Database, entrusted to the European Bioinformatics Institute, that will provide a single entry point to access all information on strains stored in any node of the network.

The central repository of the network is the animal facility at Monterotondo, near Rome, where the CNR has made available 1,750 m2 of top-class installations since April 1999 with the support of the European Commission. The center has an estimated total mouse capacity of 40,000 specimens.

On November 16, 2000, Research Commissioner Philippe Busquin launched an initiative to reinforce European activities in genome research related to human health. In the framework of this initiative, the development of new genome-based technologies, as well as new bioinformatics tools, were recognized as key factors for enabling competitive genome research and the development of new diagnostics and new therapeutic approaches.

Following the launching of the initiative, EUR 25 million were immediately earmarked to support projects dealing with post-genomics databases and suitable animal models for human health, considered essential infrastructures in the field.

The current grant being negotiated, amounting to EUR 4.5 million for two projects, is another example of research infrastructures support under this initiative, coming less than six months after its launch.

A further EUR 40 million are expected to support decisive research activities in post-genomics through a limited number of integrated projects that combine research, co-ordination and training in one single action. The projects will be selected following a competitive call before the end of this year.

These EUR 65 million will be committed in 2001 on top of the regular support for genome research activities of the Quality of Life program. In total, the Community will allocate some EUR 100 million to support genome research in 2001.

The project being negotiated with the EMMA consortium will address the most pressing demands related to the need for a solid infrastructure enabling further research, namely the networking of the participating centers and the expansion of EMMA services.

Related website:

EMMA

[Contact: Carlos Martinez-Riera, Michel Claessens]

11-Jun-2001