Mouse radiation and chemical induced deletion mutagensis

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DESCRIPTION (provided by applicant): Mouse deletion stocks are valuable resources for functional dissection of the mouse genome. Several strategies have been developed for generating mice with chromosome deletion. But all these methods are currently applied to recover deletions only around specific loci. Generation of random deletions in the genome using chemical or radiation-induced deletion directly in the mouse germline can be a powerful strategy for generating mice with inheritable deletion. However, application of this mutation strategy to genome-wide was not possible because of a lack of powerful mapping technologies. The high resolution and high throughput mouse genome scanning technology we recently developed promises to solve this mapping problem. Our mouse whole genome BAC arrays contain more than 19,000 overlapping BACs, providing a tiling path to cover the entire mouse genome. Using these arrays, the mouse genome can be scanned to reveal chromosome deletion or gain larger than 200 kb in any region of the genome by simple hybridizations without the need for breeding and phenotypic tracking as required in conventional meiotic mapping strategy. In this pilot study, we propose to apply our whole genome BAC array technology to reevaluate the feasibility of generating genome-wide mouse deletion stocks. The goal of this study is to define the optimal conditions for chemical and/or radiation induced deletion mutagenesis methods for generating mice carrying inheritable deletions.