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 of susceptibility to small intestinal cancer. Strain B10.O20 is susceptible to tumors of the small intestine induced by a transplacental treatment with the carcinogen N-ethyl-N-nitrosourea on day 18 of gestation, whereas strain O20 is completely resistant. F1 hybrid mice are also completely resistant, indicating that homozygosity of the B10.O20 allele of at least one susceptibility gene is required for the development of tumors of the small intestine. To map this gene, we used backcross 2 (N3) mice. We tested 283 [((B10.O20 x O20)F1 x B10.O20) x B10.020] N3 mice, 67 of which developed tumors of the small intestine. Their genotype was determined with the use of more than 85 simple sequence length polymorphisms (SSLPs) spread over the genome. If a SSLP is linked closely to a susceptibility gene, it is expected that almost none of the N3 mice with small intestinal tumors are heterozygous for this marker. We found that very few tumor-bearing N3 mice were heterozygous for SSLP markers on the distal part of chromosome 4 compared with the N3 mice without small intestinal tumors. This difference is highly significant (chi 2 = 31 for D4Mit158). Therefore, one of the genes that influence susceptibility to small intestinal cancer, ssic1, maps to the distal part of chromosome 4.