Creating Multi-Gene Reporter Mice Via "Recombineering"

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DESCRIPTION (provided by applicant): The specific aim of this proposal is to generate a physically linked multiple-gene-reporter mouse model that is relevant to bone biology. This animal model will have broad research applications in the field of bone biology. It will aid basic scientists in their ability to understand how cells within the bone lineage grow and differentiate. It may also be used by private industry to aid in the identification of novel compounds, which may lead to treatment of bone abnormalities, such as osteoporosis. The generation of linked multi-gene transgenic mice is novel and may influence the future design of transgenic mice. We propose to assemble a multi-gene-reporter DNA construct using Bacteria Artificial Chromosomes (BACs) and recombination technology in bacteria. A distinct feature that separates this transgenic mouse model from currently existing ones, is that the transgenic DNA construct will contain multiple gene reporter elements that are physically linked. The presence of multiple reporter genes in the same mouse has several advantages, including increasing the rate of data acquisition and the ability to identify and isolate distinct cell populations from the same mouse. As a result of linkage of the reporter genes, this mouse model can be easily crossed with other lines of mice without separation of individual reporters. As proof of concept, we have chosen three genes to drive the expression of three spectral variant fluorescent reporters to identify three distinct cell types important to bone biology. This animal model will have broad applications in research and we believe it will contribute to improvements in public health. It will aid basic scientists in their ability to understand how bone cells form, function, and interact with each other. It may also be used by private industry to aid in the identification of new drugs, which may lead to treament of bone diseases, such as osteoporosis.