MICE UNITED!
Update November 2011
GM-mice for the advancement of health and medicine. Genetically modified
mouse lines (GM-mice) are key to basic life sciences to identify roles of genes and
gene products in development, physiology and disease, and to innovative research in
Life Sciences, Agro-Food and High Tech. The creation and complex breeding of GMmice is done by research institutions (mostly public organizations) but there are
ethical and managerial challenges for more efficiency in order to avoid the production
of unnecessary surplus animals and expansion of facilities. Other concerns are
preservation of the genotypes that are key to institutional programs, and animal
health status.
Specialized and high-tech research infrastructures for the characterization and
research use of GM-mice have been developed by a dozen (semi) public research
institutions in The Netherlands. However, the exchange of animals or research data
is hampered by differences in microbiological status and conditioning of the animals,
causing delays and extra costs. In addition, as more subtle means of modification
become available (such as organ specific and/or induced expression of the altered
genotype), many lines contribute to the intended geno-/phenotype by cross-breeding,
involving many breeder animals and co-creating offspring that is off-target. In
consequence, in-house breeding by research institutions is inevitable in many cases
and traditional commercial breeders/providers cannot meet these requirements for
orchestrated breeding in a demand-driven way.
Collaboration. Typically, purpose made mouse lines are phenotyped for the
physiological and/or behavioural function of interest to the creator, but both classic
and innovative methods for broad phenotyping are indispensible to identify
unexpected phenotypes that might be of huge interest to other research groups. To
share mice between institutions is not as easy as one might think because different
conditions of hygiene and microbiological quality make exchange complicated in view
of the risk for the colony of the receiving institution. Secondly, phenotypes will result
from both nature (genetics) and nurture (upbringing, individual experiences). Early
conditioning of the animals will differ between institutions dependent on diet,
microbiological status, climate, noise levels, et cetera. Also, some animal models are
bred in different locations and this breeding can be made more efficient when
centralized. Better coordination or shared facilities will enhance harmonization, thus
potentially enhancing the outcomes and validity of broad phenotyping programs. The
project provides for the building of a network and a central facility for the production
and characterization of GM-mice.
The Roadmap application concerns the initial investment in the facilities and
services named Centre for Advanced Bioresource Services (CABS). Five public
institutions and three private companies are committed to collaborate to create both
the network and the facility, in a non-exclusive way. The (co)applicants are users
(looking for enhancement of their program) or providers (of innovative technology and
services) or a combination of both. The initiative is endorsed by a far greater circle of
associates. This will enhance competitiveness of Dutch academia and innovative
industry, and may provide a Dutch foothold of EU Infrafrontier program (no Dutch
partnership at present)., and which will allow the participating companies to export
this concept outside the Netherlands.
Infrastructure, technologies and services
The new facility will become showcase of advanced transgenic animal breeding and
phenotyping technology, which will attract international attention. The infrastructure
provides for the -investigator driven- centralized breeding, maintenance, and
cryopreservation of GM-mice as well as import services including reviving from frozen
stock or rederivation. The center will accommodate services for the characterization
of GM-mice (collection and processing of organs and tissues, automated behavioural
phenotyping). By virtue of SPF-breeding, prospective users (academia, small and
large businesses) will have facilitated access to high end technologies available
through the multicenter network (transgenesis, bioimaging, biometrics, biotelemetry,
behavioural and other phenotyping platforms) for all.
The center will contribute to the development and application of 3R-alternatives and
provide training opportunities.
Mice United-NEWS- Mice United-NEWS- Mice United- NEWS- Mice United- NEWS
An application for the NWO National Roadmap for Large-Scale Research Facilities
2011 was submitted in August and reviewed. Three out of 5 anonymous peer
reviewers scored the proposal as Excellent. The reviews were shared between the
partners and a rebuttal was sent to NWO, as requested.
Next step will be interviews, January 2012.
Meanwhile, a scientific advisory board and a supervisory board are prepared and will
be installed by the end of this year.
Most important, the Schaijk site of MSD has been secured for this project. This
comprises recently constructed animal holding rooms, procedure rooms and
associated laboratories, all up to and above standards.
Contact: m.fentener@erasmusmc.nl (main applicant)