The International Mouse Phenotyping Consortium (IMPC) is an international scientific endeavour to create and characterize the

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

of 20,000

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 importan ...

strains. Launched in September 2011, the consortium consists of over 15 research institutes across four continents with funding provided by the

NIH The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

, European national governments and the partner institutions. The initiative is projected to take 10 years (until 2021), and will focus on analysing

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

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 i ...

mice generated on an isogenic

C57BL/6 C57BL/6, often referred to as "C57 black 6", "B6", "C57" or "black 6", is a common inbred strain of laboratory mouse. It is the most widely used "genetic background" for genetically modified mice for use as models of human disease. They are the ...

N background by the

International Knockout Mouse Consortium The International Knockout Mouse Consortium (IKMC) 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 ...

. The mouse strains are characterized in a broad based phenotyping pipeline that is focused on revealing insights into human disease by measuring embryonic, neuromuscular, sensory, cardiovascular, metabolic, respiratory, haematological, and neurological parameters. The protocols used to assess these phenotypes have been standardized across the IMPC partners and are available at IMPReSS. Mouse strains generated by the IMPC partners are deposited at the KOMP repository and the European Mutant Mouse Archive. In many cases, strains carrying one of two types of alleles will be archived - a null allele used in the primary IMPC phenotyping pipeline and a conditional ready allele that allows tissue restricted knockouts via the

Cre-Lox Recombination Cre-Lox recombination is a site-specific recombinase technology, used to carry out deletions, insertions, translocations and inversions at specific sites in the DNA of cells. It allows the DNA modification to be targeted to a specific cell typ ...

and

FLP-FRT recombination In genetics, Flp-''FRT'' recombination is a site-specific recombination, site-directed recombination technology, increasingly used to manipulate an organism's DNA under controlled conditions ''in vivo''. It is analogous to Cre-Lox recombination, ...

systems. The phenotypic data is recorded in a freely accessible, fully searchable

online database In computing, a database is an organized collection of Data (computing), data or a type of data store based on the use of a database management system (DBMS), the software that interacts with end users, Application software, applications, and ...

, generating what has been described as a "comprehensive encyclopaedia of mammalian gene function."

IMPReSS

The International Mouse Phenotyping Resource of Standardised Screens (IMPReSS) coordinates and presents standardized

protocols Protocol may refer to: Sociology and politics * Protocol (politics), a formal agreement between nation states * Protocol (diplomacy), the etiquette of diplomacy and affairs of state * Etiquette, a code of personal behavior Science and technology ...

that are used by mouse research clinics to assess biological characteristics of mutant mouse strains. IMPReSS was launched in 2011 to help the IMPC achieve its goal of characterizing a knockout mouse strain for every gene and will continue to be actively developed for the ten year life-time of the project. IMPReSS, the successor of EMPReSS, is built on the concept of a "phenotype pipeline": a sequence of individual procedures performed on a mouse at a specified age and organized to minimize interference from one procedure to the next. Each procedure is broken down into a set of multiple parameters that capture both data and metadata. Data parameters are associated with biomedical

ontology Ontology is the philosophical study of existence, being. It is traditionally understood as the subdiscipline of metaphysics focused on the most general features of reality. As one of the most fundamental concepts, being encompasses all of realit ...

terms in order to facilitate data sharing and to aid in the identification of phenotypic mouse-models of human diseases.

EMPReSS

The European Mouse Phenotyping Resource for Standardized Screens (EMPReSS), the predecessor for IMPReSS, developed more than a 150 standardized protocols for the characterization of mutant mouse strains across European research institutes as part of the EUMODIC and EUMORPHIA projects. EMPReSS was actively developed from 2002 until it was superseded by IMPReSS in 2011. Phenotype data collected from EMPReSS protocols is available at Europhenome.

Embryonic-lethal knockout lines

Around 30% of all targeted gene knockouts in mice result in embryonic or

perinatal Prenatal development () involves the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal deve ...

death. The effects of these mutations cannot therefore be studied in live adult mice, except as

heterozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

mutants. However, systematic studies of embryonic-lethal knockouts are important to understand how these genes influence embryo development and survival. In 2013 the IMPC published the Bloomsbury report on mouse embryo phenotyping, outlining a standard pipeline for the screening of embryonic-lethal knockouts in homozygote mutants. In the UK, their recommendations form the basis of the DMDD (Deciphering the Mechanisms of Developmental Disorders) project.

References

{{reflist Model organism databases Genetic engineering in the United Kingdom Genetically modified organisms Science and technology in Cambridgeshire South Cambridgeshire District

IMPReSS

EMPReSS

Embryonic-lethal knockout lines

See also

References