An overall aim of the Program Project is to elucidate mechanisms of asthma using, in part, animal models. A critical feature of the SCOR is to provide transgenic and knockout and knock-in mice as appropriate models. The Transgenic Core will offer a comprehensive genetic modified animal facility including transgenic and knockout animals to the Program Project. It will also provide a "speed backcrossing" service whereby DNA polymorphisms will be used to facilitate rapid backcrossing of any given transgene or knockout onto an appropriate inbred background. The Core will also provide cryopreservation (and reconstitution of mice from frozen embryos) capabilities for the cost-effective storage of genetically modified mice. Finally, the Core will develop regulated transgenes that permit the expression of given gene products in the airways to be controlled by exogenous manipulation by the investigator.