Slide 1 - MRC Mouse Network.ppt

							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

             www.mousephenotype.org
 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

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



                          www.mousephenotype.org
 Status:
 Launch – Sept 28th 2011
Centre                                                       Total for Phase 1
MRC Harwell                                                        330
Sanger Institute                                                   1000
NIH - BASH                  Baylor, Sanger, Harwell                830
NIH - DTCC           UC Davis, TCP, Children’s Oakland, CR         830
NIH - JAX                       Jackson Lab                        830
TCP, Toronto                                                       150
Helmholtz, Munich                                                  250
ICS, Strasbourg                                                    250
Riken BRC                                                          250
MARC, Nanjing                                                      250
CNR, Monterotondo                                                  250
TOTAL                                                             5220




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


               www.mousephenotype.org
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



                 www.mousephenotype.org
                 Terminal                                                                                 In life


                                                                                             Open Field




                                                                                    9
                                                                                           Modified SHIRPA/Dysmorphology
                                                                                                                                                               7 M + 7 F Mutant Adult Mice




                                                                                         Grip Strength
     Hematology

     Clinical Blood Chemistry




                                                                                    10
                                                                                         Acoustic Starte/PPI
     Insulin Blood Level

                                                                                         Calorimetry

                                                                                    11
     FACS analysis – blood/spleen?

     Gross Pathology and Tissue Collection (2+2)




16
                                                                                         ECG / Echo
                                                                                    12

     Heart Weight

                                                                                         Intraperitoneal Glucose Tolerance Test
     Tissue Embedding and Block Banking (2+2)
                                                                                    13




                                                                                         Challenge Whole Body Plethysmography
     Histopathology (2+2)
     - from blocks where required
                                                                                                                                  Weight Curve – 4wk to 16wk




                                                                                         Auditory Brain Stem Response (2+2)
                                                                                    14




                                                                                         Body Composition (DEXA)

                                                                                         X-ray (5 + 5)




                                                                                         Slit Lamp
                                                                                    15




                                                                                         Opthalmoscope
                            Tests in
                        development or
                                                                  Mandatory tests




                      under consideration
                                            Non-mandatory tests
                                                                                                                                                                IMPC adult phenotyping pipeline
Proposed IMPC Embryonic Phenotyping
Pipeline

   IKMC mES cells (B6N)                                         ≥7 Embryos from Sub-viable Lines




                                                                                                                                                                         Dissection & gross morphology
                                                                Dissection & gross morphology
    Germline transmission




                                                                                                                                                                                                         (embryos & placentae)
                                                                                                (embryos & placentae)




                                                                                                                                                                                                                                                                      (embryos & placentae)
                                  subviable




                                                                                                                                        (embryos & placentae)




                                                                                                                                                                                                                                                     Histopathology
       Heterozygotes                              Homozygotes




                                                                                                                                                                                                                                 (iodine staining)
                                                                                                                        lacZ staining
                              <40% expected                                                                                                                     viable




                                                                                                                                                                                                                                   Embryo μCT
                               homozygous
                             mutants at weaning



       Homozygotes
                                                                                                                                                                                                                                 E14.5
            viable




                     >40% expected                                                                    E12.5
                     homozygous
                     mutants at weaning


 Adult Phenotyping Pipeline




Draft Pipeline – Under Consultation, Report Available
             (www.mousephenotype.org)
IMPC Informatics




   MPI2
   EBI, Harwell, Sanger
www.mousephenotype.org