Genetic control of polyamine-dependent susceptibility to skin tumorigenesis.
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.
Megosh
Louis C
LC
The Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, Pennsylvania 19096, USA.
Hu
Juncai
J
George
Ken
K
O'Brien
Thomas G
TG
D000818:Animals; D030801:Animals, Genetically Modified; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018895:Microsatellite Repeats; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism
D011073:Polyamines; D009955:Ornithine Decarboxylase