The Mouse Genetic Core (Core A) is an integral part ofthis effort, as it has in the past and hopefully in the future will support the work ofthe Program Project Grant by providing complex knockout mice and BAC transgenic mouse strains will serve as a repository for all newly developed mouse strains. Core A has three Specific Aims: #1 To generate novel knockout mouse strains, which will support P#1 and P#2 and based upon interactions with human studies in P#2 and P#3. #2 To generate transgenic mice based BAC clones and mutant BAC clones obtained by multi-step recombineering, which will support P#1 and P#2 and based upon interactions with human studies in P#2 and P#3. #3 To support the mutant mouse activities in P#1 and P#2, and to maintain the transgenic and knockout mouse strains used by P#1, P#2 and to facilitate treatment studies as guided by P#3. .