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Knockout mouse resource

Update: November 2007

Researchers can apply for a limited number of gene knockout mouse strains and associated phenotypic data, to be acquired from Deltagen Inc. and Lexicon Pharmaceuticals. Proposals are invited through the Wellcome Trust's funding streams as part of a research grant application and can be made via eGrants. Applications will be considered until the final funding committee in July 2008. Please bear in mind applications take four to six months to process. If you have any queries on the timing of your application, please feel free to contact the Trust.

Background

The Wellcome Trust has negotiated and will fund the acquisition of a limited number of gene knockout mouse strains and associated phenotypic data from Deltagen Inc. and Lexicon Pharmaceuticals. This resource, which will be archived and distributed through the European Mutant Mouse Archive (EMMA), will provide researchers with unprecedented access to two private collections of knockout mice, providing valuable models for the study of human disease and laying the groundwork for a public, genome-wide library of knockout mice. Such comprehensive information on such a large group of mice has never been available to public sector researchers, and is expected to greatly accelerate efforts to explore gene functions in health and disease. Under the terms of the world-wide academic licence granted to the Trust for the use of the mouse lines by Deltagen and Lexicon, researchers will be able to share the mouse lines acquired with other academic collaborators.

Two calls for proposals have already been made and 87 lines have been awarded [Excel 196KB]. These lines are currently being rederived and archived and will be made available to the research community as a whole, through EMMA, as well as to the individual researcher who submitted the proposal.

Researchers are now invited to request other Deltagen and Lexicon lines via research grant applications made through the Trust's funding streams.

What materials are available?

Researchers can request that all or parts of the following for each mouse line be made available to them directly:

  • frozen embryos
  • frozen embryonic stem cells
  • targeting vectors sequence information
  • phenotypic data
  • live mice.

No charges will be made for the materials requested but a nominal fee will be charged for shipping costs.

Who can make a proposal?

Proposals will be considered from researchers who meet the Trust's eligibility criteria.

How to apply

Applicants are invited to apply via eGrants through the relevant funding streams.

Applications can be made through the Trust's standard grant schemes. Please complete the application form [Word 100KB] and attach it as a PDF to your eGrants application.

Decisions will be made by the relevant Wellcome Trust Funding Committees until July 2008. Please bear in mind applications take four to six months to process.

Applications must provide a scientific rationale for the acquisition of the mouse line/lines justified in terms of the scientific proposal or evidence of community need.

If the grant is awarded, the order for the mouse line will be placed by EMMA, with the supplier of the specific line. The requested material will be made available to the researcher who applied for the material and the mouse lines and information will be archived at EMMA for access by other researchers. Mouse lines will be made available to researchers on the basis of a standard materials transfer agreement (see intellectual property rights, below).

What mouse lines can I apply for?

A number of lines have already been purchased by the NIH and have been deposited in repositories at the Jackson Laboratories (JAX) and the Mutant Mouse Regional Resource Centers (MMRRC) in the United States.Researchers wishing to access these lines should apply directly to these repositories in the normal way. A list of the lines purchased by the NIH is available.

Which lines are already being processed?

A list of the lines that have already been purchased [Excel 196KB] through the two previous calls for proposals is available.

How much will I pay to receive the mouse materials?

There will be a nominal cost charged by EMMA for the proposers for supply of mouse materials plus shipping costs.Researchers who subsequently order lines through EMMA would be subject their usual charges and conditions.

How long will it take before I receive the line/s and or data?

For successful applications:

  • phenotypic data will be posted on EMMA's website within four months of notification of award
  • live mice will be distributed within a minimum of eight months of notification of award
  • frozen embryos will be delivered within a minimum of 15 months of notification of award.

Each successful line will be assigned to a specific EMMA node for rederivation and archiving. Applicants will be informed which EMMA partner to contact for updated information on their specific line.

How do researchers gain access to phenotypic data obtained under the contracts?

The phenotypic data are rich and wide-ranging and are quite similar between the two companies from which the mouse lines were derived.Phenotypic data will be made available through the appropriate EMMA database and the Mouse Genome Informatics (MGI) website at the Jackson Laboratory.

Who do I contact with specific questions?

Questions about the call process and the acquisition and contracts can be made to mmc@wellcome.ac.uk.

Further information

What are knockout mice used for?

Knocking out the activity of a gene provides valuable clues about what that gene normally does. Humans share many genes with mice. Consequently, observing the characteristics of knockout mice gives researchers information that can be used to better understand how a similar gene may cause or contribute to disease in humans.

Examples of research in which knockout mice have been useful include studying and modelling different kinds of cancer, obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson's disease.

Many of these mouse models are named after the gene that has been inactivated. For example, the p53 knockout mouse is named after the p53 gene which codes for a protein that normally suppresses the growth of tumors by arresting cell division. Humans born with mutations that inactivate the p53 gene suffer from Li-Fraumeni syndrome, a condition that dramatically increases the risk of developing bone cancers, breast cancer and blood cancers at an early age.

Intellectual property rights

Mouse lines made available from EMMA to researchers will be provided subject to licence terms to use the knockout mouse materials and their progeny and derivatives and related data in the 'Field of Use'.The rights granted shall extend to breeding of mice whether within a line or with a line of different strain or genetic background.

In regard to the above terms, 'Field of Use' shall mean:

a) all teaching, research, and development activities conducted by faculty, researchers, students and other employees or individuals associated with The Wellcome Trust or any academic institution, and

b) academic research that is conducted at the facilities of an academic institution in conjunction with commercial entities; provided that the Field of Use excludes such collaborative research with commercial entities where

(i) the commercial entity financially supports such research

(ii) the commercial entity is primarily responsible for establishing the research plan

(iii) the commercial entity obtains material intellectual property rights with respect to such research, or

(iv) the academic institution does not retain material commercial rights to exploit such intellectual property.

Researchers who receive the knockout mice lines through EMMA are free to publish any results from research involving the lines and also to seek patent or other intellectual property protection for any of the inventions or discoveries resulting from such research. Any associated publications should acknowledge the support of the Wellcome Trust.

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