The Mouse Congenics Core B will provide centralized breeding for use in each of the individual projects of SAMP1/YitFc (SAMP), TNF?ARE, and control (AKR/J) mice, as well as SAMP and TNF?ARE congenic lines that carry targeted genetic deletions of key mediators of intestinal innate immunity that are relevant to the research strategies of each project. Maintaining these mouse breeding colonies and experimental animals in a common centralized facility under uniform environmental conditions continues to be crucial to the success of this Program. Centralization of mouse production also significantly reduces costs by eliminating redundant breeding colonies or the need to purchase mice commercially, and ultimately reduces the numbers of mice required by ensuring efficient utilization by each of the projects.
A second aim i s to provide centralized production of genetically-mutated SAMP and TNF?ARE mice via marker-assisted breeding to significantly shorten the time required to generate these congenic sub-strains. Transfer of induced mutations into an appropriate background can be accomplished in 5 generations using this approach.
The third aim of the core is to provide regular monitoring and internal quality control of histopathological scoring of intestinal inflammation for PPG experimental mice used in all three projects, a service that will be heavily used through the Histology/Imaging Core of the NIDDK-funded Cleveland Digestive Diseases Research Core Center (DDRCC). A centralized core component that randomly samples and re-scores intestinal sections from PPG experimental mice across all three projects and across a time-course of ages will provide a common framework for PPG quality control, as well as assist greatly in assuring standardized interpretation of data generated by each of the three projects. A strength of this component is the availability of an experienced GI pathologists, Dr. Xin, to perform the histopathological re-scoring and to provide ongoing consultative service to the projects concerning the pathological features of disease in this model. Dr. Pizarro will continue to direct the core. A committee consisting of the core director and project leaders will address routine quality control and prioritization issues. An oversight committee will review the operation of the core on a yearly basis.
Crohn's disease (CD) affects more than 700,000 individuals in the US and incurs significant costs to society. Understanding the precise mechanisms and innate immune defects that cause the disease will allow us to develop better therapies and begin to develop a cure for this devastating disease.
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