Animal Research in a Global Environment Meeting the Challenges: Proceedings of the November 2008 International Workshop (2011) / Chapter Skim
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Coordination of International Rodent Resources
Coordination of International Rodent Resources
Pages 185-214
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From page 185... ...
Coordination of International Rodent Resources
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From page 187... ...
The NIH model organism-sharing policy covers all projects that may produce model organisms with the intent that they will be made available to the research community. In 2003 NIH produced a new guide notice, that grant applications of $500,000 or more of direct costs in any single year are expected to include a plan on data sharing, meaning that the research institution and the researcher have to demonstrate to the NIH how they are going to make these resources available, be it through a material transfer agreement (MTA)
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From page 188... ...
We at the NIH found that the existing agreements did not address the uniqueness of animal models and crossbreeding issues. Therefore, we developed our specific form to transfer animals called the "Material Transfer Agreement to Transfer Organisms." It is a modified NIH standard agreement, but contains special terms.
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From page 189... ...
The animal transfer agreement is very different from a material transfer agreement. The MTA specifically deals with intellectual property issues, whereas the animal transfer agreement deals with the care and use of a particular animal and is usually signed off by the vet in the institution.
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From page 190... ...
When publishing results, if a paper is coming out describing a new knockout, it is useful to presign agreements with the mouse model on them so that when the investigator gets requests, s/he only needs to sign the agreement and ship the mouse off. As noted earlier, NIH encourages our investigators and our grantees to deposit their mice in repositories, to save time, effort, and money in their labs.
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From page 191... ...
Further, these strains can carry different mutations that mimic pathologic or disease conditions seen in humans. In the past, spontaneous genetic mutations in mice have contributed to understanding the biology of human disease in significant ways, but today's focus has shifted to induced, genetically engineered, or modified mouse strains.
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From page 192... ...
in the United States; the North American Conditional Mouse Mutagenesis (NorCOMM) Project funded by Genome Canada and its partners; and the European Conditional Mouse Mutagenesis (EUCOMM)
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From page 193... ...
The projects in North America and Europe have agreed to share their gene lists and data in order to help with the coordination. Ideally, resources produced by one project would be available to scientists on a different continent, thereby enabling scientists to simply order all mouse strains locally, thus avoiding the hassle of international transport.
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From page 194... ...
We then applied a very comprehensive set of screens or phenotyping to try to identify the expression of those mutated genes by looking for abnormal phenotypes. My contribution was from my pathology phenotyping lab, where we were using gross, histo-, and molecular pathology techniques to try to identify novel mutations or the expression of those mutations as pathology phenotypes.
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All our lines are catalogued through the international mouse strain resource, hosted by the Jackson Laboratory (JAX)
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We focus on the 2,000 genes that are available to us and are not being done by another consortium. The genes available in the pipeline are being posted at the Wellcome Trust Sanger Institute (www.sanger.ac.uk/htgt)
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The basis for the IKMC is to develop all the 22,000 protein-encoding genes in the mouse genome, in BL/6 ES cell lines. Because BL/6 ES cell lines present challenges with germline transmission, success in development, and culture conditions it is quite possible that not every lab or transgenic facility will achieve the same efficiencies with BL/6 ES cells that they have had with the more robust ES cells of the past.
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From page 198... ...
We can induce skin fibroblasts with four genetic factors to become pluripotent stem cells, develop an allelic series of mutations across a gene of interest, and provide the tools to characterize them early, to assist investigators in making the decision about whether they really need this mouse model shipped around the world or not. Also, for secondary modifications, again the models that we are characterizing, that we are depositing in our repository, have typically come through a phenotyping pipeline.
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From page 199... ...
There are also currently available 2,500 genetrap clones and over 600 clones mutated by gene targeting. The consortium is headed and coordinated by Alan Bradley and Wolfgang Wurst; Wolfgang is at our center and Alan is at the Wellcome Trust Sanger Institute.
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Distribution of the cell lines is done through our center and for the mouse lines it is through EMMA, the European Mouse Mutant Archive. Intellectual property for the gene-trap lines is handled by the tech transfer unit at our facility and at the Wellcome Trust Technology Center for the targeted lines.
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From page 201... ...
There is also EUMODIC, the European Mouse Disease Clinic, a consortium headed by Steve Brown, where we have a pilot project combining mouse clinics. Another component is EMMA, where we have currently some 1,500 mouse lines, not counting the ES cell lines.
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From page 202... ...
All materials come in with material transfer agreements to protect the intellectual property rights of the developer and to ensure their proper use by the recipient. Coinciding with the RIKEN BioResource Center, the Japanese Ministry of Education, Culture, Sports, and Science and Technology inaugurated the National Bioresource Project in 2002.
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From page 203... ...
cell lines from C57BL/6 and in some of these the germline transmission is confirmed. RIKEN also has ES cells of inbred strains from nuclear transfer, mouse induced pluripotent stem (iPS)
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Also, three years ago the Asian Mouse Mutagenesis Resources Association (AMMRA) was created to promote the mouse mutagenesis project and facilitate access to mouse strains in Asia.
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In 1990, the ILAR Committee on Preservation of Laboratory Animals was convened to discuss what could be done with repositories. Basically, the discussion addressed what could be done best with live animal preservation versus cryopreservation?
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Establish multidisciplinary teams to develop new approaches to the collection, cryopreservation, and distribution of germplasm for high-priority translational species; 3. Support research on the biosecurity of cryopreserved animal germplasm, and the detection and elimination of laboratory animal pathogens that might compromise research findings; 4.
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C.J. Peters, who was at Fort Detrick in Frederick, Maryland, in the 1980s, isolated some of the major strains of Rift Valley fever virus and did some laboratory animal experiments.
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The question, of course, at this point is, Since it behaves as a Mendelian single gene trait, which of these two sites is actually the gene and which may be the hitchhiking material? We did a quick cross and determined that, in fact, it was the bottom of chromosome 3.
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From page 209... ...
Shipping frozen material minimizes health risk at the receiving institution. However, there are some drawbacks, particularly in terms of time.
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Therefore, it is up to the shipper to understand how things move from one point to the next and what the options are if shipments are to be successful. Animals are transported in commerce every day, particularly laboratory animals between institutions.
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Live animal shipments account for less than 0.1% of all air cargo, and lab animals are an even smaller fraction of that. It may be necessary to enclose as many as 39 separate documents for transport under certain conditions; generally, however, it is less than a third of that.
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IATA's Live Animals and Perishables Board sets the standards for air transportation, which are followed by 260 airlines. Many governments and international bodies use the LAR as the primary transportation standard.
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It is better to ship germplasm if possible, but if it is necessary to ship live animals certain things are needed. The scientific community needs to engage the air carriers through IATA on issues of air carriage of lab animals.
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This monitoring process involves looking at the temperature and other environmental conditions of materials as they move through the transport system. Much of the information about transportation failures, especially with ground transportation, is anecdotal.
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