Newly available genetic tools are transforming studies of complex cellular interactions in vivo and have the potential to support rational exploration of the pathogenesis of autoimmunity in systemic lupus erythematosus (SLE). At this point, transgenic and """"""""knock-out"""""""" mutants of many relevant genes are widely available or readily generated in rodents. In addition, methods and reagents for mapping and cloning genes in both rodents and humans are now accessible through the Human Genome Project and its offshoots. In order to make these genetic tools available to the members of the SCOR for their research programs, we have designed a new Genetics Core. The goals of the Genetics Core are the following: to provide mutant genes to SCOR investigators in rodents with well- characterized and appropriate genetic backgrounds; to aid SCOR investigators in the generation of new genetic models relevant to the aims of the SCOR; and to provide a central PCR-based linkage analysis capability which will support the localization and cloning of novel genes in rodents and humans. The Genetics Core consists of a rodent quarantine/breeding facility and a genotyping facility. The quarantine and breeding units are supervised as a single, tandem facility in order to allow immediate monitoring, genotyping, and breeding of incoming animals while maintaining the 'pathogen-free' status of the vivarium. The quarantine/breeding facility supports the breeding necessary for propagation and selection of mutant genes or specified genetic traits, provides tissue sampling and phenotypic assessment of the animals based on protocols established for each project, and monitors each animal individually using a database designed to store phenotypic, genotypic, and breeding data in a searchable format. The genotyping facility provides DNA isolation and PCR-based mutation or linkage analysis using protocol,s designed in consultation with each investigator. The Director, technicians, and consultants assembled for this core are seasoned investigators who bring specific technical expertise as well as experience in the development of new techniques. Through the services of this core, SCOR members will have access to new whole-animal genetic models and methods for rapid localization of novel genes. We anticipate that the availability of this expertise will encourage expansion of biochemical and physiological studies from cell- culture systems into whole animal models, facilitating linkage of basic research with pre-clinical studies.
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