RFA on Development and Improvement of Inbred ES Cell Lines for Use
in Generation of Mouse Mutants (DA-06-009)
Letters of Intent Due: October 20, 2005
Applications Due: November 22, 2005
The purpose of this RFA is to develop C57BL/6 ES cell lines that are efficient
for high-throughput gene targeting and in successfully generating mice that
can transmit the targeted mutation through the germline, both steps being necessary
to create knockout mice on a C57BL/6 background. The research objectives for
this RFA are to develop one or more C57BL/6 ES cell line(s) that can be used
efficiently in gene targeting and in generating mice that can efficiently transmit
introduced mutations through the germline. The desired cell line(s) should
have the following characteristics: (1) attain gene targeting efficiencies,
using BAC targeting vectors, that will allow in terms of throughput and cost
efficiency, the use of a C57BL/6 ES cell line in a large scale-mutant generation
projects; (2)be feeder line-independent; (3) achieve a minimum of 25% germline
transmission in mice derived from independently targeted ES lines such that
no more than 4 clones per targeted gene need to be used to assure germline
transmission, and this should be demonstrated with a minimum of fifty unique
mutant genes; and (4) maintain totipotency, normal karyotype, and high germline
efficiency through multiple passages, such that it would be possible to expand
the mutant ES cell line–derivatives to complete the knockout of the mouse genome
and provide a standard resource of mutant ES cells for many years to come.
This funding opportunity will use the NIH U01 cooperative agreement award mechanism.
Up to $1.6 million per year for three years is to be awarded through this RFA.
It is anticipated that 1 to 3 awards will be funded in July 2006 for three years.
The full text of the RFA is available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-DA-06-009.html.