Festing M F, Lin L, Devereux T R, Gao F, Yang A, Anna C H, White C M, Malkinson A M, You M
MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester, LE1 9HN, United Kingdom.
Genomics. 1998 Oct 15;53(2):129-36. doi: 10.1006/geno.1998.5450.
Four putative quantitative trait loci (QTLs) that influence susceptibility to the induction of lung adenomas by urethane in an F2 cross between A/J and BALB/cOlaHsd have been mapped. Following microsatellite typing of mice with resistant and susceptible phenotypes at 97 microsatellite marker loci, a major locus was identified on chromosome 18 with a lod score of 15. This was responsible for an 8- to 10-fold increase in tumor multiplicity in males and females, respectively, having the AA and CC genotypes at the D18Mit188 marker locus. It mapped close to Dcc (deleted in colorectal cancer). A locus on chromosome 4 (lod score 6.5) had the resistant allele in strain A/J and the susceptible allele in BALB/c, with a 14-fold difference in tumor multiplicity between mice of the AA and CC genotypes. This mapped close to the Cdkn2a (cyclin-dependent kinase inhibitor 2A) locus, which is commonly deleted in mouse lung tumors. Two loci with smaller effects (lod scores 3.03 and 3.25) were identified on chromosomes 1 and 11. There was also significant sexual dimorphism in tumor multiplicity both among 151 F2 hybrids and among 52 mice resulting from a backcross to strain A/J, with males having higher tumor counts than females.
在A/J和BALB/cOlaHsd之间的F2杂交后代中，已定位出4个可能影响对氨基甲酸乙酯诱导肺腺瘤易感性的数量性状基因座（QTL）。在用97个微卫星标记位点对具有抗性和易感表型的小鼠进行微卫星分型后，在18号染色体上鉴定出一个主要基因座，其对数优势分数为15。在D18Mit188标记位点具有AA和CC基因型的雄性和雌性小鼠中，该基因座分别导致肿瘤多发性增加8至10倍。它定位在靠近Dcc（结直肠癌缺失基因）的位置。4号染色体上的一个基因座（对数优势分数为6.5），在A/J品系中具有抗性等位基因，在BALB/c品系中具有易感等位基因，AA和CC基因型小鼠之间的肿瘤多发性相差14倍。该基因座定位在靠近Cdkn2a（细胞周期蛋白依赖性激酶抑制剂2A）基因座的位置，该基因座在小鼠肺肿瘤中通常缺失。在1号和11号染色体上鉴定出两个效应较小的基因座（对数优势分数分别为3.03和3.25）。在151只F2杂种小鼠以及回交至A/J品系产生的52只小鼠中，肿瘤多发性也存在显著的性别二态性，雄性的肿瘤计数高于雌性。
