This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The purpose of the Microinjection Core Facility is to provide sophisticated mammalian molecular genetic services. These include the production of genetically engineered mice through introduction of DNA into zygotes as well as through injection of genetically manipulated embryonic stem cells into blastocysts (1), and the rederivation of mouse strains through implantation of embryos into foster recipients (2). Examples of applications for injection of DNA into zygotes include the generation of mice expressing a gene not normally expressed in a particular tissue or cell type, expressing mutated genes, expressing human genes in mice, or expressing additional copies of genes such as in aneuploid models (3,4). Depending on the design of the experiments, the DNA to be injected can be a plasmid carrying the coding region of a gene under control of a specific promoter, or large genomic regions carrying their own regulatory elements in vectors such as BACs, P1 clones, or YACs (5). Applications requiring the embryonic stem cell route are the creation of mouse strains carrying a null allele of the gene of interest (knock-out strains), a mutated allele of a gene (knock-in strains), defined chromosomal deletions, duplications, or translocations, or strains with conditionally altered temporal and/or spatial expression of genes (conditional knock-out) (6-10). Rederivation is necessary in two situations. First, rederivation is necessary when investigators need a mouse strain that is currently distributed only as frozen embryos. This is increasingly the case as National Mouse Mutant Resources, such as at the Jackson Laboratory, cannot maintain breeding stocks of all genetically engineered strains produced within the research community. The second case requiring rederivation occurs when investigators want to import mice from collaborating laboratories and the mice carry known pathogens. In this case, pathogens are removed through rederivation. The need for purification through rederivation is also increasing, as research laboratories exchange materials at increasing frequencies. In 1998 the Oklahoma Medical Research Foundation (OMRF) established a Microinjection Core Facility for the production of genetically engineered mice in Oklahoma. This facility makes available the sophisticated molecular engineering of the mouse to biomedical researchers throughout Oklahoma. There exists no other comparable facility within the state.A modern Mouse Microinjection Core Facility able to provide molecular genetic services adds important strengths to investigators at OMRF, at OUHSC, and to investigators throughout the state. We believe these sophisticated mammalian molecular genetics will continue to be an invaluable research tool for both basic and clinically oriented research, providing the technology for defining the pathobiology of diseases and for evaluating therapeutic efficacy in a well-developed mammalian model (11).
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