Megosh Louis C, Hu Juncai, George Ken, O'Brien Thomas G
The Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, Pennsylvania 19096, USA.
Genomics. 2002 Apr;79(4):505-12. doi: 10.1006/geno.2002.6736.
Overexpression of an ornithine decarboxylase (ODC) transgene greatly increases the susceptibility of mouse skin to carcinogen-induced tumor development. Like many phenotypes in transgenic models, this enhanced susceptibility phenotype is strongly influenced by genetic background. We have mapped tumor-modifier genes in intraspecific crosses between transgenic K6/ODC mice on a susceptible strain background (C57Bl/6J), a moderately resistant background (FVB), or a highly resistant background (C3H/HeJ). We identified several quantitative trait loci that influenced either tumor multiplicity or predisposition to the development of squamous cell carcinoma, but not both phenotypes. Because we did not use a tumor-promotion protocol to induce tumors, most of the quantitative trait loci mapped in this study are distinct from skin tumor-susceptibility loci identified previously. The use of a combined transgenic-standard strain approach to genetic analysis has resulted in detection of previously unknown genetic loci affecting skin tumor susceptibility.
鸟氨酸脱羧酶（ODC）转基因的过表达极大地增加了小鼠皮肤对致癌物诱导肿瘤发生的易感性。与转基因模型中的许多表型一样，这种增强的易感性表型受到遗传背景的强烈影响。我们在易感品系背景（C57Bl/6J）、中度抗性背景（FVB）或高度抗性背景（C3H/HeJ）的转基因K6/ODC小鼠之间的种内杂交中定位了肿瘤修饰基因。我们确定了几个影响肿瘤多样性或鳞状细胞癌发生易感性的数量性状基因座，但不是这两种表型都受影响。由于我们没有使用肿瘤促进方案来诱导肿瘤，本研究中定位的大多数数量性状基因座与先前确定的皮肤肿瘤易感性基因座不同。使用联合转基因-标准品系方法进行遗传分析已导致检测到影响皮肤肿瘤易感性的先前未知的遗传基因座。
