Amendments and Corrections to RFA-HG-05-007

"Completion of a Comprehensive Mouse Knockout Resource”

Letters of Intent Due: October 20, 2005

Applications Due: November 22, 2005

The purpose of this RFA is to solicit applications for research projects to initiate a trans-NIH program for the production of a comprehensive resource of mouse mutants in which every gene in the mouse genome has been knocked out by a null mutation marked with a reporter system of high utility. The ideal resource would be one in which all of the mutations are carried on a uniform background in strain C57BL/6, which is the strain most widely utilized by mouse researchers. But the NIH recognizes that, at present, there are certain technical problems, primarily related to low efficiency, with the use of C57BL/6 as the background strain for this type of high-throughput project. Therefore, the primary focus of this solicitation will be on construction of the mutations, and a secondary focus will be on the choice of mouse stain. However, applications that propose approaches to the cost-efficient generation of the mutations directly in strain C57BL/6 will be given preference for funding.

This RFA is being issued to further the value of the mouse as a powerful and important tool in the study of human disease. For many years, mouse mutants with phenotypes that mimic human traits have served as critical research tools in understanding the genetics underlying mammalian biology. The importance of the mouse as a model organism was indicated by the inclusion of a goal for the construction of genetic and physical maps of the mouse genome in the initial plan for the Human Genome Project (HGP). In fact, the HGP was actually able to accomplish significantly more than generating such maps of the mouse genome, and a high quality, finished sequence of the mouse genome (strain C57BL/6) will be completed by the end of 2005. Another major genomic resource for mouse research has been developed by the Mammalian Gene Collection (MGC) project ( http://mgc.nci.nih.gov/), which as of July 2005 included 15,325 full-ORF (open reading frame) cDNA clones, representing 11,501 individual mouse genes.  The goal of the MGC mouse cDNA program is to produce, by 2007, at least one full-ORF cDNA clone for each of the ~18,000 currently well-defined mouse genes.