komp meeting - nih common fund · 2011-08-11 · european conditional mouse mutagenesis program...

European Conditional

Mouse Mutagenesis

Program

Joined EUCOMM-CREATE-EUCOMMTools Meeting, July 5-7, 2011, Rome, Italy

KOMP Meeting

Wolfgang Wurst

EuMMCR/EMMA Repositories Distribution and Archiving

September 28th-29th, 2011 Washington, USA


Mouse Mutagenesis

Program

» European Mouse Mutant ´Cell Repository (EuMMCR) » Archiving and distribution of modified murine ES cells (iPS) » Archiving and distribution of gene modifying vector

» European Mouse Mutant Archive (EMMA)

» Archiving and distribution of modified mice » Resource data development » Training

» The European Infrastructure for phenotyping and archiving of model mammalian genomes (Infrafrontier)

» Pan-European coordination of infrastructure


Mouse Mutagenesis

Program

www.eummcr.org


Mouse Mutagenesis

Program

EUCOMM ES cell production & distribution numbers

1. Qu. 2008 2. Qu. 2008 3. Qu. 2008 4. Qu. 2008 1. Qu. 2009 2. Qu. 2009 3. Qu. 2009 4. Qu. 2009 1. Qu. 2010 2. Qu. 2010 3. Qu. 2010 4. Qu. 2010 1. Qu. 2011 2. Qu. 2011 3. Qu. 2011

total distribution 39 87 223 398 612 896 1180 1456 1779 2053 2447 2809 3294 3913 4437

EuMMCR clone production 62 149 290 495 735 1021 1355 1743 2171 2577 3101 3642 4230 4922 5631


Mouse Mutagenesis

Program

QC: LRPCR validation

analysed clones

542

5´3´ positive

70%

380

5´ positive

12%

65

3´positive

15%

81

negative

3%

16

•Southern Blot •287/350 (82%) validated

•3 clones per gene, over 95% likelihood to obtain correct clone

•Recommendation to order at least 3 clones



Mouse Mutagenesis

Program

EUCOMM country distribution of clones sent ou Europe Austria 1,2% Belgium 1,2% Czech Rep. 0,2% Denmark 0,9% Finland 0,7% France 3,4% Germany 14,3% Greece 0,2% Ireland 0,1% Israel 1,2% Italy 1,2% Netherlands 0,6% Spain 2,7% Sweden 0,3% Switzerland 1,5% U.K. 6,9%

t

48,6 %

14,9 %

rest of the world Australia 2,6% China 2,8% Japan 6,7% Korea South 0,9% Singapore 1,3% Taiwan 0,6%

USA & Canada USA 45,3% Canada 3,3%


Mouse Mutagenesis

Program

www.emmanet.org

Martin Hrabe de Angelis


Mouse Mutagenesis

Program

EMMA - European Mouse Mutant Archive

www.emmanet.org


Mouse Mutagenesis

Program

EMMA – Core Services: Archiving / Distribution

Live Mice Cryo Archive Live Mice

M A L E S FEMALES

IVF EF

SF

EF

Sperm

Embryos

Database

IVF

ET

ET

ET

M A L E S FEMALES

www.emmanet.org


Mouse Mutagenesis

Program

EMMA archive: Total number of submissions (September 2011)

0

500

1000

1500

2000

2500

3000

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

121

297

569

859

1096

1340

1564

2224

2563 2703

www.emmanet.org

Presenter

Presentation Notes

02-03176 03-04272 04-05290


Mouse Mutagenesis

Program

Statistics of the EMMA archive Number of requests per year (September 2011)

0

100

200

300

400

500

600

700

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

36 66 81

141

240 298

358

698 666

481

www.emmanet.org

Presenter

Presentation Notes

02-03176 03-04272 04-05290


Mouse Mutagenesis

Program

Stock requests

• A total of 951 requests have been submitted for EUCOMM lines • 748 requests were submitted before the end of 2010 • A total of 203 requests have so far been received by EMMA in 2011 • Since Jan 2011, an average of 33.8 requests have been received/month

0

200

400

600

800

1000

≤2009 2010 Jan '11 Feb '11 Mar '11 Apr '11 May '11 Jun '11

Num

ber

Month

Cumulative requests


Mouse Mutagenesis

Program

Breakdown of EUCOMM Shipments • 411 shipments in total have been sent out • 316 shipments were sent out before the end of 2010 • 95 shipments have been sent out in 2011 •The EUCOMM lines account for ~50% of the EMMA exports

0

100

200

300

400

500

≤2009 2010 Jan '11 Feb '11 Mar '11 Apr '11 May '11 Jun '11

Num

ber

Month

Cumulative shipments


Mouse Mutagenesis

Program

Global appeal • Requests have been received from 29 different countries • Europe 43.3%, USA (43.4%), rest of the world (13.3%)

Finland Poland Greece

Denmark Ireland Czech Republic

Sweden Belgium Austria

Netherlands Switzerland Spain

Italy France United Kingdom

Germany Brazil Hong Kong

India Uruguay Taiwan

Singapore Israel Australia

Korea Canada Japan

China United States


Mouse Mutagenesis

Program

Development of the EMMA Archive ~ 4000 lines by 2012

» EMMAservice project

» Archiving of 1224 mouse mutant lines

» EUCOMM / EUMODIC

» Production of 650 conditional KO mouse

mutants

» and large scale phenotyping

» Wellcome Trust Sanger Institute

» Mouse Genetics Program

» Production and phenotyping of up to 1000

mouse mutant lines

www.emmanet.org


Mouse Mutagenesis

Program

EMMA - Mutant mice for the scientific community

Summary EMMA is shaping the ERA

German EMMA node at IEG plays central role in project management

/development

Improvement of user services by technology development, database

development and database integration

EMMA archive and distribution capacity show strong growth

Capacity building to underpin further growth and sustainable funding

concept addressed by INFRAFRONTIER

www.emmanet.org


Mouse Mutagenesis

Program

Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Martin Hrabe de Angelis

www.emmanet.org 08.11.2011


Mouse Mutagenesis

Program

Infrafrontier project – key objectives

Preparation to meet increasing demands for phenotyping and

archiving – capacity building

Developing a business plan based on a sustainable funding

concept

Identification of the most suitable legal form

Providing a strategic plan for the construction phase

Reaching a legal agreement between all partners



Mouse Mutagenesis

Program

Infrafrontier: two main parts

Infrafrontier

Phenomefrontier Archivefrontier/EMMA

Systemic Phenotyping

Archiving / Distribution

+ emerging centres + emerging centres

Access to phenotyping services, data and mouse models



Mouse Mutagenesis

Program

Infrafrontier partners

08.11.2011

Infrafrontier partners

12 European Countries + Canada Research Institutions + Funding Agencies


Mouse Mutagenesis

Program

More information …….



Mouse Mutagenesis

Program


Acknowledgements HMGU / IDG Andreas Hörlein Antje Bürger Sarah Wübbel Laura Diener Kristian Scherf Mirjam Wadsack Nina Harms HMGU IDG

Wolfgang Wurst Cornelia Kaloff Claudia Seisenberger Joel Schick Denise Herold

WTSI

Bill Skarnes Wendy Bushell Vivek Iyer Tony West Barry Rosen Allan Bradley

HMGU IEG

Martin Hrabe de Angelis Michael Hagn Susan Marschall

Sonja Schick Alexander Agapov Martina Bürkle Viola Maier Carolin Wander Katharina Stiller HMGU Informatics Jens Hansen Anh-Thu Tieu Bernd Lentes


Mouse Mutagenesis

Program

The EMMA Network Shaping the European Research Area

www.emmanet.org

CNR/IBC Istituto di Biologia Cellulare, Monterotondo, Italy CNRS/CDTA Centre de Distribution, de Typage et d'Archivage animal, Orléans, France MRC/MGU Mammalian Genetics Unit, Harwell, UK Karolinska Institutet Karolinska Institutet, Stockholm, Sweden FCG/IGC Instituto Gulbenkian de Ciência , Oeiras, Portugal HMGU/IEG Institute of Experimental Genetics, Munich, Germany EMBL/EBI European Bioinformatics Institute, Hinxton, UK GIE-CERBM/ICS Institut Clinique de la Souris, Illkirch/Strasbourg, France Sanger Institute Wellcome Trust Sanger Institute, Hinxton, UK CNB/CSIC Centro Nacional de Biotecnología, Madrid, Spain Fleming Biomedical Sciences Research Center Al. Fleming, Athens, Greece OULU University of Oulu, Oulu, Finland BIAT Vetmeduni Vienna, Biomodels Austria, Vienna, Austria IMG Institute of Molecular Genetics, Prague, Czech Republic

University of Dresden F. Stewart

National Research Council G. Tocchini-Valentini

Institute Clinique de la Souris (ICS) Yann Herault

EMBL N. Rosenthal

Medical Research Council S. Brown

Helmholtz Zentrum München W. Wurst (coordinator), M. Hrabé de Angelis, AndreasHörlein

Wellcome Trust Sanger Institute A. Bradley (coordinator), W. Skarnes

University of Frankfurt H. von Melchner

Charite, University Berlin P. Ruiz


Mouse Mutagenesis

Program


Mouse Mutagenesis

Program

EUCOMM ES cell production & distribution numbers

1. Qu. 2008 2. Qu. 2008 3. Qu. 2008 4. Qu. 2008 1. Qu. 2009 2. Qu. 2009 3. Qu. 2009 4. Qu. 2009 1. Qu. 2010 2. Qu. 2010 3. Qu. 2010 4. Qu. 2010 1. Qu. 2011 2. Qu. 2011 3. Qu. 2011

distributed to EUCOMM partners 35 35 77 91 111 154 126 140 149 101 91 72 67 91 24 distributed to external users 4 13 59 84 103 130 158 136 174 173 303 290 418 528 500

EuMMCR clone production 62 87 141 205 240 286 334 388 428 406 524 541 588 692 709

KOMP2 Kickoff Meeting, September 28-30, 2011, Washington D.C.


Mouse Mutagenesis

Program

Frequency of requests

• 413 of 563 line EUCOMM lines presented on the EMMA website have been requested • 217 lines have been requested on more than one occasion • 1 to 3 requests/stock (83.3%), 4-8 requests/stock (14.8%), ≥9 requests/stock (1.9%)

0

50

100

150

200

21 16 11 10 9 8 7 6 5 4 3 2 1

Freq

uenc

y

Number of requests


Mouse Mutagenesis

Program


How many clones have been sent out per gene ?

December 2010 June 2011

orders number % number %

1 clone 298 35,9% 423 33,6%

2 clones 297 35,7% 438 34,8%

3 clones 214 25,8% 347 27,5%

4 clones 14 1,7% 32 2,5%

5 clones 8 1,0% 17 1,3%

6 clones 0 0,0% 3 0,2%

average 1.96 clones 2.04 clones


Mouse Mutagenesis

Program


EUCOMM WP9, timelines of distribution

„before“ „short“ „reasonable“ „long“ „too long“

< 0 days < 50 days 50-100 days 100 - 200 days > 200 days Jun. 2010 15,0% 42,0% 27,0% 13,4% 2,6% Dec. 2010 10,5% 46,5% 23,9% 15,4% 3,6% Jun. 2011 7,2% 46,7% 25,2% 16,0% 4,8%


Mouse Mutagenesis

Program


EUCOMM WP9, LRPCR efforts

analysed clones 5´3´ positive 5´ positive 3´positive negative

70% 12% 15% 3%

542 380 65 81 16

of the clones WP9 tested 5' and 3' LRPCR positive the WP4 results were: 5' + 3' LRPCR pass 41,0% 156 same 3' LRPCR pass, 5' LRPCR fail 53,2% 202 improved 5' LRPCR pass, 3' LRPCR fail 5,8% 22 improved

same 45,2%

improved 41,4%

different side 6,0%

worse 7,5%


Mouse Mutagenesis

Program

Most frequently requested strains EMMA ID Strain name Number of Requests EM:03851 B6J;B6N-Tyr<c-Brd> Tcf7l2<tm2a(EUCOMM)Wtsi>/Wtsi 21 EM:03875 B6J;B6N-Tyr<c-Brd> Prmt5<tm2a(EUCOMM)Wtsi>/Wtsi 16 EM:03745 B6J;B6N-Tyr<c-Brd> Kdm4b<tm1a(EUCOMM)Wtsi>/Wtsi 11 EM:04163 C57BL/6NTac-Tcf7<tm1a(EUCOMM)Wtsi>/Ics 10 EM:04148 C57BL/6NTac-Xbp1<tm1a(EUCOMM)Wtsi>/Ics 10 EM:03862 B6J;B6N-Tyr<c-Brd> Smc3<tm1a(EUCOMM)Wtsi>/Wtsi 10 EM:03736 B6J;B6N-Tyr<c-Brd> Prmt1<tm1a(EUCOMM)Wtsi>/Wtsi 10 EM:04649 C57BL/6N-Il22ra1<tm1a(EUCOMM)Wtsi>/Wtsi 9 EM:04905 C57BL/6N-Dusp4<tm1a(EUCOMM)Wtsi>/Wtsi 8 EM:04680 C57BL/6N-Mtor<tm1a(EUCOMM)Wtsi>/Wtsi 8 EM:04354 B6J;B6N-Tyr<c-Brd> Adar<tm1a(EUCOMM)Wtsi>/Wtsi 7 EM:04052 B6NDen;B6N-Setdb1<tm1a(EUCOMM)Wtsi>/Ieg 7 EM:04155 C57BL/6NTac-Jmjd5<tm1a(EUCOMM)Wtsi>/Ics 7 EM:03868 B6J;B6N-Tyr<c-Brd> Prmt7<tm1a(EUCOMM)Wtsi>/Wtsi 7 EM:04493 C57BL/6N-Ezh2<tm1a(EUCOMM)Wtsi>/Wtsi 7 EM:04578 C57BL/6N-Hira<tm1a(EUCOMM)Wtsi>/Wtsi 7 EM:04002 B6NDen;B6N-Cpeb4<tm1a(EUCOMM)Wtsi>/Cnrm 7 EM:03727 B6J;B6N-Tyr<c-Brd> Sparc<tm1a(EUCOMM)Wtsi>/Wtsi 6 EM:04096 B6NDen;B6N-Aldh2<tm1a(EUCOMM)Wtsi>/Ieg 6 EM:04548 C57BL/6NTac-Arvcf<tm1a(EUCOMM)Wtsi>/Ieg 6 EM:04584 C57BL/6NTac-Jmjd6<tm1a(EUCOMM)Wtsi>/Ieg 6 EM:03841 B6J;B6N-Tyr<c-Brd> Asxl1<tm1a(EUCOMM)Wtsi>/Wtsi 6 EM:03785 B6N;B6J-Tyr<c-Brd> Ldha<tm1a(EUCOMM)Wtsi>/Wtsi 6 EM:03996 B6NDen;B6N-Asxl1<tm1a(EUCOMM)Wtsi>/Cnrm 6 EM:04723 B6NTac;B6N-Dock10<tm1a(EUCOMM)Hmgu>/Ieg 6 EM:04084 B6NDen;B6N-Uhrf1<tm1a(EUCOMM)Wtsi>/Ieg 6 EM:04970 C57BL/6N-Optn<tm1a(EUCOMM)Wtsi>/Wtsi 6 EM:04822 B6J;B6N-Tyr<c-Brd> Sirt2<tm1a(EUCOMM)Wtsi>/WtsiCnbc 6 EM:05300 B6J;B6N-Tyr<c-Brd> Prmt5<tm2a(EUCOMM)Wtsi>/WtsiCnbc 5 EM:04470 129-Epc1<tm1a(EUCOMM)Wtsi>/WtsiH 5

Joint EUCOMM-CREATE-EUCOMMTOOLS Progress Meeting, July 5-7 , 2011, Rome


Mouse Mutagenesis

Program


komp meeting - nih common fund · 2011-08-11 · european conditional mouse mutagenesis program...

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