EUCOMM
Encyclopedia
The European Conditional Mouse Mutagenesis Program or EUCOMM is an EU
-funded program to generate a library of mutant
mouse embryonic stem cell
s for research purposes.
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.
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
. 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
).
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.
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 the IKMC site. The distribution of EUCOMM products is being handled by a separate non-commercial organisation, the European Mouse Mutant Cell Repository.
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
-funded program to generate a library of mutant
Mutant
In biology and especially genetics, a mutant is an individual, organism, or new genetic character, arising or resulting from an instance of mutation, which is a base-pair sequence change within the DNA of a gene or chromosome of an organism resulting in the creation of a new character or trait not...
mouse embryonic stem cell
Embryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...
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 embryonic stem cellEmbryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...
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
International Knockout Mouse Consortium
The International Knockout Mouse Consortium is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to create knockout mice to study...
, (an organisation including the EUCOMM, KOMP, NorCOMM and TIGM
Texas Institute for Genomic Medicine
The Texas A&M Institute for Genomic Medicine is a research institute of Texas A&M AgriLife Research. It was founded in 2005 under a $50 million award from the Texas Enterprise Fund to pioneer the development of life-changing medical breakthroughs, accelerate the pace of medical discoveries and...
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 geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
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
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
. The retrovirus inserts itself 'randomly' into the mouse genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
. When it inserts into a gene's intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
, the introduced DNA will stop that gene copy being expressed
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
, and the gene is considered to be knocked out (see gene trapping
Gene trapping
Gene trapping is a high-throughput approach that is used to introduce insertional mutations across the mammalian genome. It is performed with gene trap vectors whose principal element is a gene trapping cassette consisting of a promoterless reporter gene and/or selectable genetic marker flanked by...
).
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
Site-specific recombinase technology
Site-specific recombinase technology allows for the manipulation of genetic material in order to explore gene function. The success of the Human Genome Project has made recombinant DNA technology an inevitable next step in molecular biology and genetics. As a mechanism of DNA recombination,...
) 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 mouseKnockout mouseA knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...
)
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 the IKMC site. The distribution of EUCOMM products is being handled by a separate non-commercial organisation, the European Mouse Mutant Cell Repository.