V.8; l.9, September 2006
NIH “KOMP mutagenesis program awarded to MBP...
After nearly 3 years of planning efforts, the NIH has awarded more than $50
million in funding to several research institutes to participate in the Knockout
Mouse Project, more commonly known by its short-hand acronym, KOMP. As
announced in a September 7 press release from the NIH, the UC Davis Mouse Biology Program, in a consortium with its collaborators at the Children’s Hospital
Oakland Research Institute (CHORI) and The Sanger Institute, was awarded
approximately $23 million over 5 years to create 5000 mutant ES cell lines of
genes for which there are not yet “knockout” mice available. Regeneron, Inc.,
was awarded a similar grant to create an additional 3500 ES cell lines. What this
means is that, at the end of 5 years, the scientific community will have at least
8500 more knockout ES cell lines than are available and accessible now for
scientific research.
But wait, there’s more…All of these 8500 new knockout ES cell lines will be on
the C57BL/6 genetic background. This will be quite a feat, as there currently are
very few knockout ES cell lines on this genetic background. The major advantage
of using the “B6” line is that most investigators typically mate their “chimeras”
back to this genetic background; since most ES cell lines in use today are related
to a variety of 129 substrains, this “backcrossing” breeding strategy immediately
diminishes the “homogeneity of genetic constitution” that is the basis for the
unique and extremely valuable characteristic of inbred mouse lines used for
biomedical research. By injecting mutant B6 ES cells into B6 blastocysts, and
then breeding the resultant chimeras with wildtype B6 mice, the heterozygous
offspring remain on a pure, inbred, genetic background.
Another interesting aspect of the KOMP mutagenesis program is that the CHORISanger-
UCD team, known as the CSD consortium, will utilize a “knock-out first”
strategy by applying a technique known as targeting trapping to insert a
conditional-ready, plasmid-based knockout allele into each gene. On the other
hand, Regeneron will utilize a “definitive-null allele” strategy by replacing the
entire (or a significantly large segment) of each gene with a BAC-based dual
reporter-selection cassette.
Finally, and probably most importantly, the KOMP “products”…besides ES cells,
also DNA targeting constructs, live mice, frozen embryos, data and protocols, will
be made available and accessible to the scientific community as rapidly as
possible after the “products” have been made and verified. During the first year of
the KOMP, UCD and Regeneron will be responsible for posting an on-line catalog
and ordering system, with the assistance of the KOMP Database Coordinating
related materials. Then, beginning sometime during the Summer of 2007, the
NIH will make its final KOMP award to establish the KOMP Repository which will
takeover archive and distribution responsibilities from the CSD consortium andRegeneron. Stay tuned…considering its success with the MMRRC, UCD hopes to play a significant role in
hosting and operating the KOMP Repository!
EUCOMM and NorCOMM also take shape
Our colleagues in Canada and in the European Union have already begun their own KOMP-like initiatives that will nicely complement the US efforts. The EU's EUCOMM (European Conditional Mouse Mutagenesis) Programme and Canada's NorCOMM (North American Conditional Mouse Mutagenesis) Project will both produce an additional 12,000 to 20,000 new mutant ES cells and a significant number of mice that, together with the KOMP products, should create an unprecedented set of resources for the scientific community. And the MBP will be able to assist investigators to obtain products from both the EUCOMM and NorCOMM projects…the MBP is a co-PI on the NorCOMM project, and is working with the leadership of EUCOMM to transfer a complete copy of their ES cell collection to UCD to facilitate distribution to research scientists in the US and Pacific Rim.
SIGTR collection headed to the UCD-MMRRC!
After a lengthy period of negotiation, the leadership of the Sanger Institute Gene Trap Resource ( SIGTR ) and the UCD-MMRRC have come to an agreement to place a complete copy of the SIGTR gene trap collection of nearly 12,000 gene trap ES cell clones at the UCD-MMRRC for archiving and distribution to the US and Pacific Rim scientific community. Now, researchers in this part of the world will be able to look up, find, and order SIGTR gene trap ES cell lines on the MMRRC website and get rapid delivery. And, just as we do for our existing BayGenomics and Soriano libraries , the UCD-MMRRC will offer microinjection services to convert an ES cell clone into live mice, upon request. We have just now begun to receive cell lines from the SIGTR collection, and hope to have them all safely in our archive and prepared for distribution by January 1, 2007. Stay tuned!....
Mouse repatriation efforts continue
The KOMP, EUCOMM, and NorCOMM mutagenesis efforts intend to create gene knockouts for genes not yet known to have been mutated. But what about those mouse lines that have been published as knockouts, but are neither available nor accessible in the public domain? Well, with a large NIH grant to UCD, we are pursuing those mouse lines and placing them in public repositories, such as our own MMRRC , and the IMR, for distribution. Repatriation efforts of privately held mutant mice, as well as significant portions of collections from commercial producers , are being made available to the scientific community. You can search the IMSR to find if your mutant mouse of interest is available as a result of this ongoing repatriation effort. And if you are interested in having your mouse placed in the public domain for distribution, contact us at www.mmrrc.org and let us know!...we'll take it from there.
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