The Animal Models Core centralizes breeding, development and maintenance of extremely useful, but complex mouse and zebrafish models by providing a stable environment for each centrally housed line to increase efficiency, decrease costs and prevent phenotype variation. This Core leverages exceptional specific pathogen free (SPF) and gnotobiotic mice and zebrafish facilities and expert personnel to provide high-quality resources and services to all 3 current and proposed Projects. Core A personnel work closely with Project investigators to provide SPF and gnotobiotic mouse and zebrafish models that are essential to accomplish goals of each of the current projects. This core provides prioritized creation of novel SPF mouse strains and derivation of germ-free (GF) lines that will support the success of Projects 1, 2, 3 and 4. In addition, this Core has created highly innovative zebrafish models to facilitate activities in Projects 3 and 4. By providing technical experience and central housing to create and maintain GF wild type, mutant and double mutant mouse strains, Core A allows investigators to efficiently perform innovative, mechanistic experiments far beyond the resources of traditional R01-supported investigators and extends the capabilities of our national gnotobiotic resource. These GF mice and zebrafish allows Project investigators to manipulate the complex gut microbial ecology to study the mechanistic role of luminal microbes on immune and epithelial responses in gnotobiotic animals colonized with defined microbiota. The Specific Aims of the Animal Models Core are to provide P01 Projects with: 1.Centralized breeding of specific pathogen free and germ-free mice and zebrafish to eliminate redundancy in breeding units, diminish expenses, decrease environmental variation by maintaining central housing facilities and minimize waste by promoting shared utilization of animals by multiple investigators; 2.Create new mouse and zebrafish models including importing existing mutant strains for central breeding, creating new strains, including cell-specific mutants by crossbreeding of existing mutant, transgenic and fluorescent protein reporter lines, and generating new transgenic and mutant lines; 3.Germ-free derivation of existing and new mouse strains that can be used to evaluate the impact of complex resident microbiota individual microbial species or microbial consortia on intestinal inflammation and mucosal homeostasis. This Core supports Projects 1, 2, 3 and 4 in the renewal application.