New chemically induced skin tumour susceptibility loci identified in a mouse backcross between FVB and dominant resistant PWK.
BACKGROUND
A variety of skin cancer susceptibility among mouse strains has allowed identification of genes responsible for skin cancer development. Fifteen Skts loci for skin tumour susceptibility have been mapped so far by using the two-stage skin carcinogenesis model [induced by 7.12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)]. A few responsible genes have been identified using wild-derived dominant resistant Mus spretus mice, and one has been confirmed as a low penetrance cancer susceptibility gene in a variety of human cancers.


RESULTS
In the present study, we found that wild-derived PWK mice developed no tumour by treatment with the two-stage skin carcinogenesis protocol. This phenotype is dominant resistant when crossed with the highly susceptible strain FVB. By analyzing the F1 backcross generation between PWK and FVB, we found empirical evidence of significant linkage at the new loci Skts-fp1 on chromosome 4 and suggestive linkage on chromosomes 1, 3, 11, 12 and 14 for skin tumour susceptibility. Skts-fp1 includes the Skts7 interval, which was previously mapped by a Mus spretus and NIH backcross. We also observed suggestive linkage on chromosomes 1 and 2 in the female population only, while suggestive linkage on chromosomes 14 and 15 only was observed in the male population. A significant genetic interaction was seen between markers of D11Mit339 and D16Mit14.


CONCLUSIONS
Analysis of this new cross may facilitate the identification of genes responsible for mouse skin cancer susceptibility and may reveal their biological interactions.
Fujiwara
Kyoko
K
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. kyoko.fujiwara@roswellpark.org <kyoko.fujiwara@roswellpark.org>
Igarashi
Jun
J
Irahara
Natsumi
N
Kimura
Makoto
M
Nagase
Hiroki
H
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000187:drug effects; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000235:genetics; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics*; D040641:Quantitative Trait Loci; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate
D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate