de Boer J G, Erfle H, Holcroft J, Walsh D, Dycaico M, Provost S, Short J, Glickman B W
Center for Environmental Health, University of Victoria, BC, Canada.
Mutat Res. 1996 Jun 10;352(1-2):73-8. doi: 10.1016/0027-5107(95)00254-5.
The finding of a large discordance between animal species in their response to a carcinogenic challenge, has led to the realization that the useful extrapolation of animal test data to humans requires a better understanding of animal interspecies differences. With the development of transgenic shuttle vector based animal systems we are now able to study mutation of the same genetic target in both mice and rats. We have begun to analyze mutants recovered from rat lines carrying low copy numbers of the same lambda/lacI constructs carried by the Big Blue mouse. A large database on mutations in lacI transgenic mice is already available for comparison. The data indicate that the differences between the mutations recovered from rat liver and germ cell tissues are similar to those recovered from transgenic mice, but when compared with a large database of mutations available for mice, some site-to-site differences may exist. This study represents the first interspecies look into the molecular nature of mutations in the lacI transgenic rodents.
动物物种在对致癌挑战的反应上存在很大差异，这一发现使人们意识到，要将动物试验数据有效地外推到人类，需要更好地理解动物种间差异。随着基于转基因穿梭载体的动物系统的发展，我们现在能够在小鼠和大鼠中研究同一遗传靶点的突变。我们已经开始分析从携带与“大蓝”小鼠相同低拷贝数λ/lacI构建体的大鼠品系中回收的突变体。关于lacI转基因小鼠突变的大型数据库已经可供比较。数据表明，从大鼠肝脏和生殖细胞组织中回收的突变之间的差异与从转基因小鼠中回收的差异相似，但与可用于小鼠的大型突变数据库相比，可能存在一些位点间差异。这项研究首次对lacI转基因啮齿动物突变的分子性质进行了种间研究。
