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.