The purpose of the Mouse Core will be to provide a centralized service-oriented facility to insure the capacity of each participating project to produce and maintain transgenic and gene-disrupted mice. The mouse core will also serve the projects of this Program by supporting the infrastructure of the BUXCO system for making invasive resistance and compliance measurements in mice, which will be utilized by most projects. The mouse core will also carry out airway dissections that will be utilized by each project. As all projects propose to utilize a combination of these services, the Mouse Core will be an important part of this Program Project Grant. The transgenic/knockout production unit is supported by dedicated space within our animal facility and is fully equipped. In addition, the Holtzman laboratory routinely utilizes the BUXCO system and carries out isolations of mouse airways, and a technician in his laboratory who is proficient in these techniques will be the individual doing these experiments for projects in this Program. This core was developed in our Pulmonary Division in 1995 and has been extensively utilized by Project Investigators, Co-Investigators, and Core Leaders on this application for many years (Holtzman, Green, Brody, Walter, Shipley). It is staffed by personnel with a collective extensive track record of expertise and productivity in this area. The core has been responsible for generating well over 100 separate transgenic and knockout lines, with multiple founders/chimeras of each. Many of the mice which have been and will be made by this core will further serve to facilitate collaborative interactions amongst Project Leaders. The Mouse Core is currently also supported in part by another Program Project Grant (Robert M. Senior, PI) and SCOR grant (Michael J. Holtzman, PI). The core is also utilized by other investigators at Washington University. Thus, this will allow us to realize an economy of scales and lower production costs per mouse generated.