Mouse Genetics Project

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The Mouse Genetics Project (MGP) is a large-scale mutant mouse production and phenotyping programme aimed at identifying new model organisms of disease. [1] [2] [3] [4]

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Based at the Wellcome Trust Sanger Institute, the project uses knockout mice most of which were generated by the International Knockout Mouse Consortium. For each mutant line, groups of seven male and seven female mice move through a standard analysis pipeline aimed at detecting traits that differ from healthy C57BL/6 mice. [1] The pipeline collects many measurements of viability, fertility, body weight, infection, hearing, morphology, haematology, behaviour, blood chemistry and immunity and compares them to wild type controls using a statistical mixed model. [5] These data are immediately shared among the scientific and medical research community through a bespoke open access database, [6] and summaries are displayed in other online resources, including the Mouse Genome Informatics database and the Wikipedia-based Gene Wiki. [4]

As of July 2013, the MGP reports having over 900 mutant lines openly available to the international research community, [4] and have "substantively complete" analysis for over 650 mutant lines, [6] of which over 75 per cent have at least one abnormal phenotype. [1] Among these are new discoveries of genes implicated in disease, including finding:

See also

References

  1. 1 2 3 Ayadi A, Birling MC, Bottomley J, et al. (October 2012). "Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics Project". Mamm. Genome . 23 (9–10): 600–10. doi:10.1007/s00335-012-9418-y. PMC   3463797 . PMID   22961258.
  2. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica . 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. S2CID   85911512.
  3. 1 2 van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol . 12 (6): 224. doi: 10.1186/gb-2011-12-6-224 . PMC   3218837 . PMID   21722353.
  4. 1 2 3 White JK, Gerdin AK, Karp NA, et al. (July 2013). "Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes". Cell . 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC   3717207 . PMID   23870131.
  5. ↑ Karp NA, Melvin D, Mott RF (2012). "Robust and sensitive analysis of mouse knockout phenotypes". PLoS ONE . 7 (12) e52410. Bibcode:2012PLoSO...752410K. doi: 10.1371/journal.pone.0052410 . PMC   3530558 . PMID   23300663.
  6. 1 2 Mouse Resources Portal, Wellcome Trust Sanger Institute.
  7. ↑ Alderton GK (March 2011). "Genomic instability: Expanding the reach of Fanconi anaemia". Nat. Rev. Cancer . 11 (3): 158–159. doi:10.1038/nrc3027. PMID   21451554. S2CID   26277627.
  8. ↑ Crossan GP, van der Weyden L, Rosado IV, Langevin F, Gaillard PH, McIntyre RE, Gallagher F, Kettunen MI, Lewis DY, Brindle K, Arends MJ, Adams DJ, Patel KJ (February 2011). "Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia". Nat. Genet. 43 (2): 147–52. doi:10.1038/ng.752. PMC   3624090 . PMID   21240276.
  9. ↑ Bassett JH, Gogakos A, White JK, Evans H, Jacques RM, van der Spek AH, Ramirez-Solis R, Ryder E, Sunter D, Boyde A, Campbell MJ, Croucher PI, Williams GR (2012). "Rapid-throughput skeletal phenotyping of 100 knockout mice identifies 9 new genes that determine bone strength". PLoS Genet. 8 (8) e1002858. doi: 10.1371/journal.pgen.1002858 . PMC   3410859 . PMID   22876197.
  10. ↑ McIntyre RE, Lakshminarasimhan Chavali P, Ismail O, Carragher DM, Sanchez-Andrade G, Forment JV, Fu B, Del Castillo Velasco-Herrera M, Edwards A, van der Weyden L, Yang F, Ramirez-Solis R, Estabel J, Gallagher FA, Logan DW, Arends MJ, Tsang SH, Mahajan VB, Scudamore CL, White JK, Jackson SP, Gergely F, Adams DJ (2012). "Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies Seckel syndrome". PLOS Genet. 8 (11) e1003022. doi: 10.1371/journal.pgen.1003022 . PMC   3499256 . PMID   23166506.
  11. ↑ Nijnik A, Clare S, Hale C, Chen J, Raisen C, Mottram L, Lucas M, Estabel J, Ryder E, Adissu H, Adams NC, Ramirez-Solis R, White JK, Steel KP, Dougan G, Hancock RE (July 2012). "The role of sphingosine-1-phosphate transporter Spns2 in immune system function". J. Immunol. 189 (1): 102–11. doi:10.4049/jimmunol.1200282. PMC   3381845 . PMID   22664872.
  12. ↑ Nijnik A, Clare S, Hale C, Raisen C, McIntyre RE, Yusa K, Everitt AR, Mottram L, Podrini C, Lucas M, Estabel J, Goulding D, Adams N, Ramirez-Solis R, White JK, Adams DJ, Hancock RE, Dougan G (February 2012). "The critical role of histone H2A-deubiquitinase Mysm1 in hematopoiesis and lymphocyte differentiation". Blood . 119 (6): 1370–9. doi: 10.1182/blood-2011-05-352666 . PMID   22184403.
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