GENETIC IDENTIFICATION OF MOM-1, A MAJOR MODIFIER LOCUS AFFECTING MIN-INDUCED INTESTINAL NEOPLASIA IN THE MOUSE
GENETIC IDENTIFICATION OF MOM-1, A MAJOR MODIFIER LOCUS AFFECTING MIN-INDUCED INTESTINAL NEOPLASIA IN THE MOUSE
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DOI：
10.1016/0092-8674(93)90484-8
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发表时间：
1993-11-19
期刊：
影响因子：
64.5
通讯作者：
DOVE, W
中科院分区：
文献类型：
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作者：
DIETRICH, WF;LANDER, ES;DOVE, W
人类APC基因突变可引起多种家族性结肠癌综合征。多发性肠瘤（Multiple intestinal neoplasia, Min）小鼠为家族性结肠癌提供了一个很好的模型：它携带突变的小鼠Apc基因，并发生多种肠腺瘤。在这里，我们分析了这种肿瘤表型是如何被遗传背景显著改变的。我们报告了在Min/+动物中强烈改变肿瘤数量的基因座的遗传定位。这个名为Mom-1 （Min-1的修饰因子）的基因定位于4号染色体的远端，在两个种内回交中控制着约50%的肿瘤数量遗传变异。LOD评分大于14时支持映射。有趣的是，Mom-1位于与人类染色体1p35-36的同源性保护区域，该区域在包括结肠肿瘤在内的多种人类肿瘤中经常发生体细胞杂合性缺失。这些结果提供了影响遗传性癌症综合征表达的主要修饰因子的证据。
Mutations in the human APC gene cause various familial colon cancer syndromes. The Multiple intestinal neoplasia (Min) mouse provides an excellent model for familial colon cancer: it carries a mutant mouse Apc gene and develops many intestinal adenomas. Here, we analyze how this tumor phenotype is dramatically modified by genetic background. We report the genetic mapping of a locus that strongly modifies tumor number in Min/+ animals. This gene, Mom-1 (Modifier of Min-1), maps to distal chromosome 4 and controls about 50% of genetic variation in tumor number in two intraspecific backcrosses. The mapping is supported by a LOD score exceeding 14. Interestingly, Mom-1 lies in a region of synteny conservation with human chromosome 1p35-36, a region of frequent somatic loss of heterozygosity in a variety of human tumors, including colon tumors. These results provide evidence of a major modifier affecting expression of an inherited cancer syndrome.