Rationale: The current PPG proposal is highly dependent on the generation and maintenance of transgenic mice, gene deficient """"""""knockout) mice, and hybrid transgenic-knockout mice for the proposed studies on surfactant homeostasis. The transgenic-knockout mice for the proposed studies on surfactant homeostasis. The transgenic mouse core is designed to take advantage of established expertise of the Children's Hospital Research Foundation in the generation and analysis of transgenic mice for the study of lung disease. This core will: 1) generate additional novel transgenic mice and gene targeted mice required to extend our understanding of surfactant homeostasis in surfactant deficiency and injury response; 2) breed and maintain these genetically modified mice for the individual projects in a sterile barrier isolation facility to assure a pathogen free environment which is necessary for accurate interpretation of experiments. The animal core program provides continuous monitoring of sentinel mice to assure pathogen free status of animals and provides dedicated laminar hoods and sterile work environment for manipulation of mice. These functions are critical to providing long term supply of pathogen free genotyped mice for projects 1-3. The pro-nuclear microinjection to produce transgenic mice and embryonic stem cell to blastocyst transfer facility has been in continuous operation at the Children's Hospital Research Foundation for over seven years and produced several of the transgenic and knockout mouse models utilized in the current PPG.
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