Gould K A, Dove W F
McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin, Madison, USA.
Exp Lung Res. 1998 Jul-Aug;24(4):437-53. doi: 10.3109/01902149809087379.
Although the methodology for mapping genes controlling susceptibility to tumor development in mice is becoming well established, it remains a formidable challenge to move from linkage to locus. Positional cloning, now commonly used in the identification of loci affecting a qualitative phenotype, has yet to be successfully applied to quantitative trait loci. This study describes the application of candidate gene testing, a method complementary to positional cloning. The method has been applied to evaluate candidates for the quantitative trait locus, Mom1, which modifies the susceptibility of ApcMin/+ mice to spontaneous intestinal tumor development. The authors also discuss the further testing of one candidate, the phospholipase gene Pla2g2a, by transgenesis. Finally, studies on the mode of action of Mom1 are discussed in light of the evidence that Mom1 encodes this secretory phospholipase.
尽管在小鼠中定位控制肿瘤发生易感性的基因的方法已日趋成熟,但从连锁分析过渡到确定基因座仍然是一项艰巨的挑战。位置克隆目前常用于鉴定影响定性表型的基因座,但尚未成功应用于数量性状基因座。本研究描述了候选基因检测方法的应用,这是一种与位置克隆互补的方法。该方法已用于评估数量性状基因座Mom1的候选基因,Mom1可改变ApcMin/+小鼠自发性肠道肿瘤发生的易感性。作者还讨论了通过转基因对一个候选基因——磷脂酶基因Pla2g2a进行进一步检测。最后,鉴于Mom1编码这种分泌性磷脂酶的证据,讨论了关于Mom1作用模式的研究。