Kras-2 alleles, mutations, and lung tumor susceptibility in the mouse--an evaluation.
Lung Tumor Susceptibility (LTS) in the mouse has been shown to be influenced by loci within the Major Histocompatibility Complex (MHC) and the Kras-2 regions. In crosses between susceptible and resistant strains, one allele of Kras-2 has been linked with a high LTS, whereas the other allele has been linked with a low LTS. Furthermore, these Kras-2 alleles affect differently the occurrence of Kras-2 mutations in lung tumors. In this study we evaluated the relationship between LTS, Kras-2 alleles and Kras-2 mutations, using Recombinant Congenic Strains with identical MHC haplotypes. The Kras-2 region indeed influences the frequency of Kras-2 mutations in N-ethyl-N-nitrosourea-induced lung tumors. These mutations are associated with larger tumors. However, Kras-2 affects LTS only marginally. Several strains with identical Kras-2 alleles and mutation frequency differ widely in LTS, while some strains with different alleles and mutation frequency do not. We conclude that a considerable part of the genetic variability in LTS is caused by LTS-loci other than Kras-2 and MHC.
Fijneman
R J
RJ
The Netherlands Cancer Institute, Division of Molecular Genetics, Amsterdam.
Ophoff
R A
RA
Hart
A A
AA
Demant
P
P
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D004198:Disease Susceptibility; D005260:Female; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*