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International Mouse Phenotyping Consortium

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International Mouse Phenotyping Consortium
Content
DescriptionEncyclopaedia of phenotypes from knockout mice.
OrganismsMouse
Contact
Primary citationBrown and Moore, 2012
Release date2011
Access
Websitehttp://www.mousephenotype.org

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

IMPReSS
Content
DescriptionStandardized protocols for phenotyping mutant mouse strains.
OrganismsMouse
Contact
Primary citationBrown and Moore, 2012
Release date2012
Access
Websitehttp://www.mousephenotype.org/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.

See also

References

  1. ^ Brown SD, Moore MW (May 2012). "Towards an encyclopaedia of mammalian gene function: the International Mouse Phenotyping Consortium". Dis. Models Mech. 5 (3): 289–92. doi:10.1242/dmm.009878. PMC 3339821. PMID 22566555.
  2. Brown SD, Moore MW (October 2012). "The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping". Mamm. Genome. 23 (9–10): 632–40. doi:10.1007/s00335-012-9427-x. PMC 3774932. PMID 22940749.
  3. Morgan H, Simon M, Mallon AM (2012). "Accessing and mining data from large-scale mouse phenotyping projects". Int. Rev. Neurobiol. International Review of Neurobiology. 104: 47–70. doi:10.1016/B978-0-12-398323-7.00003-3. ISBN 9780123983237. PMID 23195311.
  4. Schofield PN, Hoehndorf R, Gkoutos GV (May 2012). "Mouse genetic and phenotypic resources for human genetics". Hum. Mutat. 33 (5): 826–36. doi:10.1002/humu.22077. PMC 3473354. PMID 22422677.
  5. ^ "IMPReSS International Mouse Phenotyping Resource of Standardised Screens". Mousephenotype.org. Retrieved 2013-08-01.
  6. "Knockout Mouse Project (KOMP) Repository". KOMP. 2010-08-01. Retrieved 2013-08-01.
  7. "EMMA - the European Mouse Mutant Archive". Emmanet.org. Archived from the original on 2013-08-12. Retrieved 2013-08-01.
  8. "IMPC | International Mouse Phenotyping Consortium". Mousephenotype.org. Retrieved 2013-08-01.
  9. ^ "Empress". Empress.har.mrc.ac.uk. Archived from the original on 2011-03-20. Retrieved 2013-08-01.
  10. Brown, S. D. M.; Chambon, P.; De Angelis, M. H.; Eumorphia, C. (2005). "EMPReSS: Standardized phenotype screens for functional annotation of the mouse genome". Nature Genetics. 37 (11): 1155. doi:10.1038/ng1105-1155. PMID 16254554.
  11. Mallon, A. -M.; Blake, A.; Hancock, J. M. (2007). "EuroPhenome and EMPReSS: Online mouse phenotyping resource". Nucleic Acids Research. 36 (Database issue): D715–D718. doi:10.1093/nar/gkm728. PMC 2238991. PMID 17905814.
  12. Chen, C. K.; Mungall, C. J.; Gkoutos, G. V.; Doelken, S. C.; Köhler, S.; Ruef, B. J.; Smith, C.; Westerfield, M.; Robinson, P. N.; Lewis, S. E.; Schofield, P. N.; Smedley, D. (2012). "MouseFinder: Candidate disease genes from mouse phenotype data". Human Mutation. 33 (5): 858–866. doi:10.1002/humu.22051. PMC 3327758. PMID 22331800.
  13. "Eumodic". Eumodic. Archived from the original on 2011-07-04. Retrieved 2013-08-01.
  14. "EUMORPHIA". Archived from the original on July 3, 2012. Retrieved July 8, 2013.
  15. ^ Adams, D; Baldock, R; Bhattacharya, S; Copp, AJ; Dickinson, M; Greene, NDE; Henkelman, M; Justice, M; Mohun, T; Murray, SA; Pauws, E; Raess, M; Rossant, J; Weaver, T; West, D (May 2013). "Bloomsbury report on mouse embryo phenotyping: recommendations from the IMPC workshop on embryonic lethal screening". Disease Models and Mechanisms. 6 (3): 571–579. doi:10.1242/dmm.011833. PMC 3634642. PMID 23519032.
  16. Mohun, T; Adams, DJ; Baldock, R; Bhattacharya, S; Copp, AJ; Hemberger, M; Houart, C; Hurles, ME; Robertson, E; Smith, JC; Weaver, T; Weninger, W (May 2013). "Deciphering the Mechanisms of Developmental Disorders (DMDD): a new programme for phenotyping embryonic lethal mice". Disease Models and Mechanisms. 6 (3): 562–566. doi:10.1242/dmm.011957. PMC 3634640. PMID 23519034.
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