Mouse radiation and chemical induced deletion mutagensis

描述(由申请人提供)：小鼠缺失库是对小鼠基因组进行功能解剖的宝贵资源。已经开发了几种策略来产生染色体缺失的小鼠。但目前所有这些方法都只应用于恢复特定基因座附近的缺失。在小鼠种系中直接使用化学或辐射诱导的缺失来产生基因组中的随机缺失可能是产生具有遗传缺失的小鼠的有效策略。然而，由于缺乏强大的作图技术，这种突变策略不可能应用于全基因组。我们最近开发的高分辨率和高通量的小鼠基因组扫描技术有望解决这一映射问题。我们的小鼠全基因组BAC阵列包含19,000多个重叠的BAC，提供了一条覆盖整个小鼠基因组的平铺路径。使用这些阵列，可以扫描小鼠基因组，以揭示染色体缺失或通过简单的杂交在基因组的任何区域获得大于200kb的染色体，而不需要像传统的减数分裂图谱策略所要求的育种和表型跟踪。在这项初步研究中，我们建议应用我们的全基因组BAC阵列技术来重新评估产生全基因组小鼠缺失库的可行性。本研究的目的是确定化学和/或辐射诱导的缺失突变方法的最佳条件，以产生携带可遗传缺失的小鼠。

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.