International Mouse Phenotyping Consortium

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International Mouse Phenotyping Consortium
International Mouse Phenotyping Consortium logo.jpg
Content
DescriptionEncyclopaedia of phenotypes from knockout mice.
Organisms Mouse
Contact
Primary citationBrown and Moore, 2012 [1]
Release date2011
Access
Website http://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. [1] [2] [3] Launched in September 2011, [1] the consortium consists of over 15 research institutes across four continents with funding provided by the NIH, European national governments and the partner institutions. [4]

Contents

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. [1] [5] The protocols used to assess these phenotypes have been standardized across the IMPC partners and are available at IMPReSS. [5]

Mouse strains generated by the IMPC partners are deposited at the KOMP repository [6] and the European Mutant Mouse Archive. [7] 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, [8] generating what has been described as a "comprehensive encyclopaedia of mammalian gene function." [1]

IMPReSS

IMPReSS
Content
DescriptionStandardized protocols for phenotyping mutant mouse strains.
Organisms Mouse
Contact
Primary citationBrown and Moore, 2012 [1]
Release date2012
Access
Website http://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. [1] 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. [9] [10] [11] 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. [12]

EMPReSS

The European Mouse Phenotyping Resource for Standardized Screens (EMPReSS), [9] 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 [13] and EUMORPHIA [14] 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. [15] 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, [15] 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. [16]

See also

Related Research Articles

Lethal alleles are alleles that cause the death of the organism that carries them. They are usually a result of mutations in genes that are essential for growth or development. Lethal alleles may be recessive, dominant, or conditional depending on the gene or genes involved.

<span class="mw-page-title-main">TRPC4AP</span> Protein-coding gene in the species Homo sapiens

Trpc4-associated protein is a protein that in humans is encoded by the TRPC4AP gene.

<span class="mw-page-title-main">BAZ1B</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein kinase, or Bromodomain adjacent to zinc finger domain, 1B (BAZ1B) is an enzyme that in humans is encoded by the BAZ1B gene.

<span class="mw-page-title-main">JARID2</span> Protein-coding gene in the species Homo sapiens

Protein Jumonji is a protein that in humans is encoded by the JARID2 gene. JARID2 is a member of the alpha-ketoglutarate-dependent hydroxylase superfamily.

<span class="mw-page-title-main">ATPAF2</span> Protein-coding gene in the species Homo sapiens

ATP synthase mitochondrial F1 complex assembly factor 2 is an enzyme that in humans is encoded by the ATPAF2 gene.

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 create knockout mice to study. Many of the targeted alleles are designed so that they can generate both complete and conditional gene knockout mice. The IKMC was initiated on March 15, 2007, at a meeting in Brussels. By 2011, Nature reported that approximately 17,000 different genes have already been disabled by the consortium, "leaving only around 3,000 more to go".

Europhenome is a resource for presenting, searching and analysing mouse phenotypes that were revealed by high throughput mouse phenotyping programmes such as EUMODIC.

The European Conditional Mouse Mutagenesis Program or EUCOMM is an EU-funded program to generate a library of mutant mouse embryonic stem cells for research purposes.

<span class="mw-page-title-main">TRIM45</span> Protein-coding gene in the species Homo sapiens

tripartite motif containing 45, also known as TRIM45, is a human gene.

<span class="mw-page-title-main">MTFMT</span> Protein-coding gene in the species Homo sapiens

Mitochondrial methionyl-tRNA formyltransferase is a protein that in humans is encoded by the MTFMT gene.

<span class="mw-page-title-main">SLC41A3</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 41, member 3 is a protein that in humans is encoded by the SLC41A3 gene.

A knockout mouse, or knock-out mouse, is a genetically modified mouse 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 important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function.

<span class="mw-page-title-main">PLD5</span> Protein-coding gene in the species Homo sapiens

Phospholipase D family, member 5 is a protein that in humans is encoded by the PLD5 gene.

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Glutamyl-tRNA(Gln) amidotransferase, subunit C homolog (bacterial) is a protein that in humans is encoded by the GATC gene. The gene is also known as 15E1.2 and encodes part of a Glu-tRNA(Gln) amidotransferase enzyme.

<span class="mw-page-title-main">C2orf54</span> Protein-coding gene in the species Homo sapiens

Chromosome 2 open reading frame 54, otherwise known as Mab21L4, is a protein that in humans is encoded by the C2orf54 gene. The orthologue in mice is 2310007B03Rik.

RIKEN cDNA 4932414N04 is a protein that in the house mouse is encoded by the 4932414N04Rik gene. The gene is also known as RP23-459M13.1.

RIKEN cDNA 4933425L06 is a protein that in the house mouse is encoded by the 4933425L06Rik gene.

RIKEN cDNA 2010107G12 is a protein that in the house mouse is encoded by the 2010107G12Rik gene. The gene is also known as Gm468.

The Mouse Genetics Project (MGP) is a large-scale mutant mouse production and phenotyping programme aimed at identifying new model organisms of disease.

References

  1. 1 2 3 4 5 6 7 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. 1 2 "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. 1 2 "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. 1 2 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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