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]
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:
- Mutation of SLX4 causes a new type of Fanconi anemia.[3][7][8]
- Nine new genes that influence bone strength.[9]
- Mutation of CENPJ models Seckel syndrome.[10]
- SPNS2 is important in mammalian immune system function.[11]
- MYSM1 is important for hematopoiesis and lymphocyte differentiation.[12]
See also
editReferences
edit- ^ a b c 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.
- ^ 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.
- ^ a b 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.
- ^ a b c 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.
- ^ 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.
- ^ a b Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
External links
edit- The Sanger Mouse Portal, containing all MGP data
- The MGP Biomart, for extracting phenotypic data