SPONTANEOUS MUTATIONS IN A LACZ TRANSGENE AND IN RELATION TO DEVELOPMENT & AGING

据推测，体细胞突变是一个主要的致病因素 衰老和与年龄相关的疾病，如癌症和动脉粥样硬化。 最近，基于穿梭载体的转基因小鼠模型已经被用于研究。 开发了能够准确定量和表征 体内突变。 这项建议的长远目标是 使用这些小鼠模型来获得更多关于突变频率的见解， 它们在发育和体内的诱导机制 衰老 该项目的具体目标是确定自发和 在小鼠的几个器官和组织中的诱发突变谱， 不同年龄水平的不同转基因品系， 胚胎发生 在整个研究中使用的转基因小鼠模型系统 项目是不同的基于CD 2和C57 B1/6的含有LacZ的细胞系 噬菌体λ和质粒载体中的突变靶基因。 对于每条线，这些向量以头到尾的排列进行整合 在基因组的不同位置 自发突变频率将 使用已建立的程序在合适的细菌宿主中测定; 所获得的突变体的代表性部分将进一步 以测序为特征。

It has been hypothesized that somatic mutations are a major causal factor in aging and age-related diseases such as cancer and atherosclerosis. Recently, shuttle vector-based transgenic mouse models have been developed that allow accurate quantitation and characterization of mutations in vivo. The broad long-term objective of this proposal is to use these mouse models to obtain more insight in mutation frequency and their mechanism of induction in relation to development and in vivo aging. The specific aim of this project is to determine spontaneous and induced mutation spectra in several organs and tissues of mice from different transgenic strains at different age-levels including embryogenesis. The transgenic mouse model systems used throughout this project are different CD2 and C57B1/6-based lines harboring LacZ mutational target genes in bacteriophage lambda and plasmid vectors. These vectors are integrated in a head-to-tail arrangement, for each line at a different site in the genome. Spontaneous mutation frequency will be determined in suitable bacterial hosts using established procedures; a representative part of the mutants obtained will be further characterized by sequencing.