A GENE FOR SUSCEPTIBILITY TO SMALL-INTESTINAL CANCER, SSIC1, MAPS TO THE DISTAL PART OF MOUSE CHROMOSOME-4

Mouse inbred strains B10.O20 and O20 were used to study the genetics o f susceptibility to small intestinal cancer. Strain B10.O20 is suscept ible to tumors of the small intestine induced by a transplacental trea tment with the carcinogen N-ethyl-N-nitrosourea on day 18 of gestation , whereas strain O20 is completely resistant. F-1 hybrid mice are also completely resistant, indicating that homozygosity of the B10.O20 all ele of at least one susceptibility gene is required for the developmen t of tumors of the small intestine. To map this gene, we used backcros s 2 (N3) mice. We tested 283 [((B10.O20 x O20)F-1 x B10.O20) x B10.O20 ] N3 mice, 67 of which developed tumors of the small intestine, Their genotype was determined with the use of more than 85 simple sequence l ength polymorphisms (SSLPs) spread over the genome. If a SSLP is linke d closely to a susceptibility gene, it is expected that almost none of the N3 mice with small intestinal tumors are heterozygous for this ma rker. We found that very few tumor-bearing N3 mice were heterozygous f or SSLP markers on the distal part of chromosome 4 compared with the N 3 mice without small intestinal tumors. This difference is highly sign ificant (chi(2) = 31 for D4Mit158). Therefore, one of the genes that i nfluence susceptibility to small intestinal cancer, ssic1, maps to the distal part of chromosome 4.