Animal models of genetic disease allows discoveries made at the molecular level, to be studied in complex, interactive, in vivo systems. The affected biological pathways can be examined in detail and compared with the pathological findings which lead to the phenotyped observed. The knockout mouse Cftr/mlUNC/mlUNC, generated by disruption of the gene for CF, lacked the Cftr protein and afforded researchers the first opportunity to perform this type of analysis in the study of CF. Using this original animal model phenotype analysis demonstrated, that despite having an identical genetic defect, mice had different phenotypes depending on their background strain. In our labs we have three lines of these mice, along with a gastrointestinal phenotype (Cftr/mlUNC/mlUNC, those with a gastrointestinal and liver phenotype Bc Cftr/mlUNC/mlUNC. The Animal Core will provide the services to run the breeding program, genotype and provide specialized care for these animals. In order to effect long-term survival of the homozygous animals they must be genotyped and identified by weaning and fed a mouse liquid diet. They must be examined daily to identify early symptoms of bowel obstruction and treated to ensure they do not die an inhumane death from bowel obstruction. This core will provide all these services and will enable the researchers to have a ready supply of animals on any of the three backgrounds. A database of homozygous animals will be maintained, updated weekly and circulated electronically to the researchers so that they can select the animals they require and arrange to share animals and tissues if appropriate.
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