Ryan J, Barker P E, Nesbitt M N, Ruddle F H
Department of Biology, Yale University, New Haven, CT 06510.
J Natl Cancer Inst. 1987 Dec;79(6):1351-7.
An Eco-RI restriction fragment length polymorphism occurring in a DNA fragment containing the first exon of the murine KRAS2 gene was shown to correlate with the inherited susceptibility of inbred strains of mice to urethan (CAS: 51-79-6)-induced pulmonary adenomas. Eco-RI digestion of murine DNA yielded four KRAS2-specific fragments. Polymorphic variation occurred in the smallest molecular-weight fragment with alleles of either 0.70 or 0.55 kb in size. Genotyping of 14 inbred strains of mice revealed a correlation between KRAS2 Eco-RI polymorphic variation and the differential susceptibility among inbred strains to development of pulmonary adenomas. Strains with a high incidence of pulmonary adenomas, either spontaneously occurring or in response to carcinogen induction, had the 0.55-kb KRAS2 allele whereas adenoma-resistant strains had the 0.70-kb allele. Analysis of a series of recombinant inbred strains (AXB, BXA) that developed from reciprocal crosses between a highly susceptible strain (A/J) and a highly resistant strain (C57BL/6J) revealed a statistically significant threefold difference in lung tumor susceptibility on the basis of KRAS2 genotype. Further analysis of individual F2 mice of a C57BL/6 female X A/J male cross also demonstrated a threefold difference in tumor susceptibility on the basis of KRAS2 allelic variation.
在包含小鼠KRAS2基因第一外显子的DNA片段中出现的一种Eco - RI限制性片段长度多态性，被证明与近交系小鼠对氨基甲酸乙酯（CAS：51 - 79 - 6）诱导的肺腺瘤的遗传易感性相关。小鼠DNA经Eco - RI酶切产生四个KRAS2特异性片段。最小分子量片段出现多态性变异，等位基因大小分别为0.70 kb或0.55 kb。对14个近交系小鼠进行基因分型，结果显示KRAS2 Eco - RI多态性变异与近交系小鼠对肺腺瘤发生的易感性差异之间存在相关性。肺腺瘤高发的品系，无论是自发发生还是对致癌物诱导有反应，都具有0.55 kb的KRAS2等位基因，而抗腺瘤品系则具有0.70 kb的等位基因。对一系列由高敏感品系（A/J）和高抗性品系（C57BL/6J）相互杂交产生的重组近交系（AXB、BXA）进行分析，结果显示基于KRAS2基因型，肺肿瘤易感性存在统计学上显著的三倍差异。对C57BL/6雌性×A/J雄性杂交的单个F2小鼠进一步分析也表明，基于KRAS2等位基因变异，肿瘤易感性存在三倍差异。
