Fijneman R J, Ophoff R A, Hart A A, Demant P
The Netherlands Cancer Institute, Division of Molecular Genetics, Amsterdam.
Oncogene. 1994 May;9(5):1417-21.
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.
小鼠的肺肿瘤易感性（LTS）已被证明受主要组织相容性复合体（MHC）和Kras - 2区域内的基因座影响。在易感和抗性品系之间的杂交中，Kras - 2的一个等位基因与高LTS相关，而另一个等位基因与低LTS相关。此外，这些Kras - 2等位基因对肺肿瘤中Kras - 2突变的发生有不同影响。在本研究中，我们使用具有相同MHC单倍型的重组近交系评估了LTS、Kras - 2等位基因和Kras - 2突变之间的关系。Kras - 2区域确实影响N - 乙基 - N - 亚硝基脲诱导的肺肿瘤中Kras - 2突变的频率。这些突变与更大的肿瘤相关。然而，Kras - 2对LTS的影响仅微乎其微。几个具有相同Kras - 2等位基因和突变频率的品系在LTS上差异很大，而一些具有不同等位基因和突变频率的品系则没有。我们得出结论，LTS中相当一部分遗传变异性是由Kras - 2和MHC以外的LTS基因座引起的。
