Identification of an X-linked locus modifying mouse skin tumor susceptibility.
The enhancing effect of overexpression of an ornithine decarboxylase (Odc) transgene on skin tumor susceptibility can be modified by genetic loci present in several inbred mouse strains. The BALB/cJ strain is among the most resistant strains so far examined; tumor multiplicity following 7,12-dimethylbenz(a)anthracene (DMBA) treatment is reduced by 90% when the K6/ODC transgene is expressed on a BALB/cJ background versus the susceptible C57BL/6J background. Further, transgenic BALB/cJ males developed more tumors than females, indicating the presence of sex-dependent modifier pathway. Analysis of 263 F2 intercross mice revealed significant linkage of markers on the X chromosome to tumor multiplicity. This analyses as well as a similar genome-wide scan of 136 backcross mice found evidence for other modifier loci on chromosomes 4, 6, and 17. Identification of these modifier genes should reveal the effector pathways responsive to Odc overexpression that mediate susceptibility to skin tumorigenesis.
George
Kenneth
K
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA.
Iacobucci
Audrey
A
Uitto
Jessica
J
O'Brien
Thomas G
TG
D000818:Animals; D014408:Biomarkers, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D015870:Gene Expression / Q000235:genetics; D050172:Genes, X-Linked / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008297:Male; D051379:Mice; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D019076:Transgenes / Q000235:genetics
D014408:Biomarkers, Tumor