The European Conditional Mouse Mutagenesis Program or EUCOMM is an EU-funded program to generate a library of

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

mouse

embryonic stem cell Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist ...

s for research purposes.

Setup

The EUCOMM program is funded by the European Union sixth R&D programme to make a library of mutant mouse

clones (ES cells), to enable the mouse research community to rapidly create mutant mice with specific mutant genes. The EUCOMM consortium is a member of the International Knockout Mouse Consortium, (an organisation including the EUCOMM, KOMP, NorCOMM and TIGM consortia) which reflects a commitment to share and promote their products and technology with the international research community.

Stem cell creation

Each stem cell contains one mutant

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

copy and one 'wild-type' (normal) gene copy. The entire library is intended to mutate 13,000 genes in total. Of these 13000 mutant genes, 8000 mutations in mouse ES Cells are 'targeted': that is, the mutation which knocks out gene function is inserted precisely into the genome. The remaining 5000 mutations are derived from 'gene-traps'. These mutations are created by infecting ES Cells with an appropriately modified retrovirus. The retrovirus inserts itself 'randomly' into the mouse

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...

. When it inserts into a gene's intron, the introduced DNA will stop that gene copy being expressed, and the gene is considered to be knocked out (see

gene trapping Gene trapping is a high-throughput approach that is used to introduce insertional mutations across an organism's genome. Method Trapping is performed with gene trap vectors whose principal element is a gene trapping cassette consisting of a prom ...

). The mutations introduced in the ES Cells are ''conditional'': this means that the initial mutation can be modified - by the application of particular DNA-altering enzymes ( site specific recombinases) to make the knockout initially ''latent'' in the genome. The gene can be later knocked out (inactivated) at a specific time-point or tissue-type in mutant mice derived from the mutant ES Cells, by appropriate breeding to other transgenic mice. This conditionality is a ''key'' property of the entire resource, and it allows a more nuanced study of the effects of the gene-knockout.

Use of stem cells

The purpose of this library is to enable the mouse research community to rapidly create mutant mice, by * selecting the stem cell (with the appropriate mutant gene) from the EUCOMM library and then * breeding a knockout mouse from that ES Cell (see

Knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importa ...

) The broad aim of the project is to facilitate research into gene function in mice (and so by inference in humans) by removing the high technical entry barrier of making the mutant ES Cells. The 8000 genes selected for mutation in mouse ES cells were drawn from the total set of protein coding mouse genes, based on a rough metric of how easy the genes were to mutate, with the technologies present at the time the project started. More 'target' genes were subsequently added to the list. All products from the program, as well links to the EUCOMM products for specific genes are available from th
IKMC
site. The distribution of EUCOMM products is being handled by a separate non-commercial organisation, the European Mouse Mutant Cell Repository.

References

External links

EUCOMM websiteEuropean Mouse Mutant Cell RepositoryIKMC
{{DEFAULTSORT:EUCOMM European Union and science and technology FP6 projects