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
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
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, Childrens 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)
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, Childrens 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
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
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
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)


subviable
Histopathology
Heterozygotes Homozygotes
(iodine staining)
lacZ staining
<40% expected viable
Embryo CT
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

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The International Mouse Phenotyping

See Skarnes et al.

Undertake broad based primary phenotyping of 20,000

Phase I (2011-2016): phenotype up to 5,000 lines

Phase II (2016-2021): Phenotype 15,000 mutants

Data freely available through a Data Coordination

Phenotyping Protocol working groups established end of

Discussion Forum on IMPC website

Second series of calls 9th December 12th January

IMPReSS (International Mouse Phenotyping Resource of

Clinical Blood Chemistry

Gross Pathology and Tissue Collection (2+2)

Intraperitoneal Glucose Tolerance Test

Challenge Whole Body Plethysmography

Auditory Brain Stem Response (2+2)

Body Composition (DEXA)

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

Dissection & gross morphology

(embryos & placentae)

(embryos & placentae)

(embryos & placentae)

>40% expected E12.5

Adult Phenotyping Pipeline

Draft Pipeline Under Consultation, Report Available

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