International Mouse Phenotyping Consortium

The International Mouse Phenotyping Consortium (IMPC) is an international scientific endeavour to create and characterize the phenotype of 20,000 knockout mouse strains. Launched in September 2011, the consortium consists of over 15 research institutes across four continents with funding provided by the NIH, European national governments and the partner institutions.

The initiative is projected to take 10 years (until 2021), and will focus on analysing homozygous mutant mice generated on an isogenic C57BL/6N background by the International Knockout Mouse Consortium. 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 and FLP-FRT recombination systems.

The phenotypic data is recorded in a freely accessible, fully searchable online database, 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 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 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 death. The effects of these mutations cannot therefore be studied in live adult mice, except as heterozygote 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.