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The International Mouse Phenotyping Consortium An Encyclopedia of Mammalian Gene Function

The International Mouse Phenotyping Consortium An Encyclopedia of Mammalian Gene Function. IMPC Alleles IKMC - EUCOMM/KOMP. Knockout- first, conditional-ready allele:. See Skarnes et al. Nature , July BL/6N ES cells. IMPC Activities.

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The International Mouse Phenotyping Consortium An Encyclopedia of Mammalian Gene Function

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  1. The International Mouse Phenotyping ConsortiumAn Encyclopedia of Mammalian Gene Function

  2. IMPC AllelesIKMC - EUCOMM/KOMP • Knockout-first, conditional-ready allele: See Skarnes et al. Nature, July BL/6N ES cells

  3. IMPC Activities • Undertake broad based primary phenotyping of 20,000 mutants from the IKMC resource • A coordinated effort of mouse clinics worldwide • Phase I (2011-2016): phenotype up to 5,000 lines • Pipeline development, logistics • Phenotyping technology developments e.g. imaging • Ramp up • Phase II (2016-2021): Phenotype 15,000 mutants • Data freely available through a Data Coordination Centre, supported by R&D groups at clinics

  4. www.mousephenotype.org

  5. IMPC 22 Academic, Government Institutes • MRC Harwell (Steve Brown, current Chair Steering Comm.; Tom Weaver) • Sanger Institute (Allan Bradley, Dave Adams, Karen Kennedy) • NIH KOMP2 • BASH, Baylor (Monica Justice) • DTCC (UC Davis (Kent Lloyd), TCP, Charles River, Children’s Hospital Oakland RI) • Jackson Lab (Karen Svenson) • Toronto Centre for Phenogenomics (Colin McKerlie) • Helmholtz Zentrum Munich (Martin Hrabe de Angelis) • Institut Clinique de la Souris (Yann Herault) • Australian Phenomics Network (Adrienne McKenzie) • RIKEN BioResource Center (Yuichi Obata) • MARC (Xiang Gao) • CNR (Glauco Toccinni Valentini) • EBI (Paul Flicek) • Secretariat (Mark Moore, Executive Director; JoergRossbacher) • FUNDERS • MRC (Nathan Richardson, Clare Newland) • NIH (Jane Peterson, Eric Green, Jim Battey, Colin Fletcher, Martin Guyer) • Wellcome Trust (Michael Dunn, Clare McVicker) • Infrafrontier(Martin Hrabe de Angelis) • Genome Canada (Cindy Bell) • European Commission (Observer status) • Canadian Institutes of Health Research, CIHR (Jane Aubin)

  6. Status: Launch – Sept 28th 2011

  7. Phenotyping Working Group Barca Meeting SOP Discussions LacZ Fertility & Viability SHIRPA/Dysmorphology Open Field Grip Strength/Startle, PPI ECG/Echo Calorimetry/IPGTT ABR Body Composition/X-ray Slit lamp/Ophthalmoscope Hematology/Clin Chem/Insulin Heart Wt./Gross Pathology/Block Banking FACS, IGs • March 2011 • Representatives from Clinics • External Experts • Secondary Screeners • Industry

  8. Phenotyping Protocols • Phenotyping Protocol working groups established end of October 2011 • 13 Working groups (22 Protocols) • Discussion Forum on IMPC website • Protocol Discussions • Series of conference calls to discuss the protocols (31st October 2011 – 8th November 2011) • InfraComp/IMPC Meeting – 14th-15th November • Second series of calls 9th December – 12th January • IMPReSS (International Mouse Phenotyping Resource of Standardised Screens) database released end of January

  9. IMPC adult phenotyping pipeline 7 M + 7 F Mutant Adult Mice Weight Curve – 4wk to 16wk In life Challenge Whole Body Plethysmography Intraperitoneal Glucose Tolerance Test Modified SHIRPA/Dysmorphology Auditory Brain Stem Response (2+2) Body Composition (DEXA) Acoustic Starte/PPI Open Field Opthalmoscope Grip Strength X-ray (5 + 5) Calorimetry ECG / Echo Slit Lamp 9 10 11 13 15 12 14 Mandatory tests Non-mandatory tests Tests in development or under consideration Gross Pathology and Tissue Collection (2+2) Tissue Embedding and Block Banking (2+2) Terminal Histopathology (2+2) - from blocks where required FACS analysis – blood/spleen? Clinical Blood Chemistry Insulin Blood Level Heart Weight Hematology 16

  10. Proposed IMPC Embryonic Phenotyping Pipeline IKMC mES cells (B6N) ≥7 Embryos from Sub-viable Lines Germline transmission subviable Dissection & gross morphology (embryos & placentae) Dissection & gross morphology (embryos & placentae) Heterozygotes Homozygotes viable <40% expected homozygous mutants at weaning Histopathology (embryos & placentae) lacZ staining (embryos & placentae) Embryo μCT (iodine staining) Homozygotes E14.5 >40% expected homozygous mutants at weaning E12.5 viable Adult Phenotyping Pipeline Draft Pipeline – Under Consultation, Report Available (www.mousephenotype.org)

  11. IMPC Informatics MPI2 EBI, Harwell, Sanger

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